Angiotensin II contributes to renal fibrosis independently of Notch pathway activation
Recent studies have described that the Notch signaling pathway is activated in a wide range of renal diseases. Angiotensin II (AngII) plays a key role in the progression of kidney diseases. AngII contributes to renal fibrosis by upregulation of profibrotic factors, induction of epithelial mesenchyma...
Gespeichert in:
| Veröffentlicht in: | PloS one 2012-07, Vol.7 (7), p.e40490 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 7 |
| container_start_page | e40490 |
| container_title | PloS one |
| container_volume | 7 |
| creator | Lavoz, Carolina Rodrigues-Diez, Raquel Benito-Martin, Alberto Rayego-Mateos, Sandra Rodrigues-Diez, Raúl R Alique, Matilde Ortiz, Alberto Mezzano, Sergio Egido, Jesús Ruiz-Ortega, Marta |
| description | Recent studies have described that the Notch signaling pathway is activated in a wide range of renal diseases. Angiotensin II (AngII) plays a key role in the progression of kidney diseases. AngII contributes to renal fibrosis by upregulation of profibrotic factors, induction of epithelial mesenchymal transition and accumulation of extracellular matrix proteins. In cultured human tubular epithelial cells the Notch activation by transforming growth factor-β1 (TGF-β1) has been involved in epithelial mesenchymal transition. AngII mimics many profibrotic actions of TGF-β1. For these reasons, our aim was to investigate whether AngII could regulate the Notch/Jagged system in the kidney, and its potential role in AngII-induced responses. In cultured human tubular epithelial cells, TGF-β1, but not AngII, increased the Notch pathway-related gene expression, Jagged-1 synthesis, and caused nuclear translocation of the activated Notch. In podocytes and renal fibroblasts, AngII did not modulate the Notch pathway. In tubular epithelial cells, pharmacological Notch inhibition did not modify AngII-induced changes in epithelial mesenchymal markers, profibrotic factors and extracellular matrix proteins. Systemic infusion of AngII into rats for 2 weeks caused tubulointerstitial fibrosis, but did not upregulate renal expression of activated Notch-1 or Jagged-1, as observed in spontaneously hypertensive rats. Moreover, the Notch/Jagged system was not modulated by AngII type I receptor blockade in the model of unilateral ureteral obstruction in mice. These data clearly indicate that AngII does not regulate the Notch/Jagged signaling system in the kidney, in vivo and in vitro. Our findings showing that the Notch pathway is not involved in AngII-induced fibrosis could provide important information to understand the complex role of Notch system in the regulation of renal regeneration vs damage progression. |
| doi_str_mv | 10.1371/journal.pone.0040490 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1325436144</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A477113581</galeid><doaj_id>oai_doaj_org_article_2a5b7e3483a54e2f92d6fd9529d0714c</doaj_id><sourcerecordid>A477113581</sourcerecordid><originalsourceid>FETCH-LOGICAL-c758t-851f1fc7b6da4386aee604f281c408cc2b420ca5593ca995f49f65626fe5d4473</originalsourceid><addsrcrecordid>eNqNkluL1DAYhoso7rr6D0QLguDFjDm2zY0wLB4Kiwse9jakadJm6CQ1SVfn35txussUFCSQhOT53ny8ebPsOQRriEv4dusmb8WwHp1VawAIIAw8yM4hw2hVIIAfnuzPsichbAGguCqKx9kZQiVDmMLz7GZjO-OissHYvK5z6Wz0ppmiCnl0uVfpiVybxrtgQm5sq0aVJhuHfe50_tlF2eejiP1Psc-FjOZWROPs0-yRFkNQz-b1Ivv-4f23y0-rq-uP9eXmaiVLWsVVRaGGWpZN0QqSehNKFYBoVEFJQCUlaggCUlDKsBSMUU2YLmiBCq1oS0iJL7KXR91xcIHPlgQOMaIEF5CQRNRHonViy0dvdsLvuROG_zlwvuPCRyMHxZGgTakwqbCgRCHNUFvollHEWlBCIpPWu_m1qdmpViYbvBgWossba3reuVuOMUPJ7yTwahbw7sekQvxHyzPVidSVsdolMbkzQfINKUsIMa1gotZ_odJo1c6kb1TapPNFwZtFweGr1a_YiSkEXn_98v_s9c2SfX3C9koMsQ9umA45CEuQHEGZ0hS80vfOQcAPmb5zgx8yzedMp7IXp67fF92FGP8G8V_xjg</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1325436144</pqid></control><display><type>article</type><title>Angiotensin II contributes to renal fibrosis independently of Notch pathway activation</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Public Library of Science (PLoS)</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Lavoz, Carolina ; Rodrigues-Diez, Raquel ; Benito-Martin, Alberto ; Rayego-Mateos, Sandra ; Rodrigues-Diez, Raúl R ; Alique, Matilde ; Ortiz, Alberto ; Mezzano, Sergio ; Egido, Jesús ; Ruiz-Ortega, Marta</creator><contributor>Chatziantoniou, Christos</contributor><creatorcontrib>Lavoz, Carolina ; Rodrigues-Diez, Raquel ; Benito-Martin, Alberto ; Rayego-Mateos, Sandra ; Rodrigues-Diez, Raúl R ; Alique, Matilde ; Ortiz, Alberto ; Mezzano, Sergio ; Egido, Jesús ; Ruiz-Ortega, Marta ; Chatziantoniou, Christos</creatorcontrib><description>Recent studies have described that the Notch signaling pathway is activated in a wide range of renal diseases. Angiotensin II (AngII) plays a key role in the progression of kidney diseases. AngII contributes to renal fibrosis by upregulation of profibrotic factors, induction of epithelial mesenchymal transition and accumulation of extracellular matrix proteins. In cultured human tubular epithelial cells the Notch activation by transforming growth factor-β1 (TGF-β1) has been involved in epithelial mesenchymal transition. AngII mimics many profibrotic actions of TGF-β1. For these reasons, our aim was to investigate whether AngII could regulate the Notch/Jagged system in the kidney, and its potential role in AngII-induced responses. In cultured human tubular epithelial cells, TGF-β1, but not AngII, increased the Notch pathway-related gene expression, Jagged-1 synthesis, and caused nuclear translocation of the activated Notch. In podocytes and renal fibroblasts, AngII did not modulate the Notch pathway. In tubular epithelial cells, pharmacological Notch inhibition did not modify AngII-induced changes in epithelial mesenchymal markers, profibrotic factors and extracellular matrix proteins. Systemic infusion of AngII into rats for 2 weeks caused tubulointerstitial fibrosis, but did not upregulate renal expression of activated Notch-1 or Jagged-1, as observed in spontaneously hypertensive rats. Moreover, the Notch/Jagged system was not modulated by AngII type I receptor blockade in the model of unilateral ureteral obstruction in mice. These data clearly indicate that AngII does not regulate the Notch/Jagged signaling system in the kidney, in vivo and in vitro. Our findings showing that the Notch pathway is not involved in AngII-induced fibrosis could provide important information to understand the complex role of Notch system in the regulation of renal regeneration vs damage progression.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0040490</identifier><identifier>PMID: 22792351</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Activation ; Angiotensin ; Angiotensin II ; Angiotensin II - administration & dosage ; Angiotensin II - toxicity ; Angiotensins ; Animals ; Apoptosis ; Biology ; Bone morphogenetic proteins ; Calcium-Binding Proteins - genetics ; Calcium-Binding Proteins - metabolism ; Cell Line ; Cellular biology ; Development and progression ; Diabetes ; Disease Models, Animal ; Epithelial cells ; Epithelial Cells - drug effects ; Epithelial Cells - metabolism ; Epithelial-Mesenchymal Transition - drug effects ; Epithelial-Mesenchymal Transition - genetics ; Extracellular matrix ; Fibroblasts ; Fibroblasts - drug effects ; Fibroblasts - metabolism ; Fibrosis ; Gene expression ; Gene Expression Regulation - drug effects ; Genes ; Human behavior ; Humans ; Hydronephrosis - genetics ; Hydronephrosis - metabolism ; Hypertension ; Hypertension - chemically induced ; Hypertension - genetics ; Hypertension - metabolism ; Intercellular Signaling Peptides and Proteins - genetics ; Intercellular Signaling Peptides and Proteins - metabolism ; Jagged-1 Protein ; Kidney - drug effects ; Kidney - metabolism ; Kidney - pathology ; Kidney diseases ; Kidney Tubules - drug effects ; Kidney Tubules - metabolism ; Kidneys ; Laboratories ; Ligands ; Male ; Medicine ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Mesenchyme ; Mice ; Mice, Inbred C57BL ; Nephrology ; Notch protein ; Notch1 protein ; Nuclear transport ; Pharmacology ; Podocytes - drug effects ; Podocytes - metabolism ; Proteins ; Rats ; Receptor, Angiotensin, Type 1 - metabolism ; Receptors, Notch - genetics ; Receptors, Notch - metabolism ; Regeneration ; Rodents ; Serrate-Jagged Proteins ; Signal Transduction ; Signaling ; Smooth muscle ; Stem cells ; Transforming Growth Factor beta1 - biosynthesis ; Transforming Growth Factor beta1 - pharmacology ; Transforming growth factor-b1 ; Transforming growth factors ; Translocation ; Vascular endothelial growth factor</subject><ispartof>PloS one, 2012-07, Vol.7 (7), p.e40490</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Lavoz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Lavoz et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-851f1fc7b6da4386aee604f281c408cc2b420ca5593ca995f49f65626fe5d4473</citedby><cites>FETCH-LOGICAL-c758t-851f1fc7b6da4386aee604f281c408cc2b420ca5593ca995f49f65626fe5d4473</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392235/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392235/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22792351$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Chatziantoniou, Christos</contributor><creatorcontrib>Lavoz, Carolina</creatorcontrib><creatorcontrib>Rodrigues-Diez, Raquel</creatorcontrib><creatorcontrib>Benito-Martin, Alberto</creatorcontrib><creatorcontrib>Rayego-Mateos, Sandra</creatorcontrib><creatorcontrib>Rodrigues-Diez, Raúl R</creatorcontrib><creatorcontrib>Alique, Matilde</creatorcontrib><creatorcontrib>Ortiz, Alberto</creatorcontrib><creatorcontrib>Mezzano, Sergio</creatorcontrib><creatorcontrib>Egido, Jesús</creatorcontrib><creatorcontrib>Ruiz-Ortega, Marta</creatorcontrib><title>Angiotensin II contributes to renal fibrosis independently of Notch pathway activation</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Recent studies have described that the Notch signaling pathway is activated in a wide range of renal diseases. Angiotensin II (AngII) plays a key role in the progression of kidney diseases. AngII contributes to renal fibrosis by upregulation of profibrotic factors, induction of epithelial mesenchymal transition and accumulation of extracellular matrix proteins. In cultured human tubular epithelial cells the Notch activation by transforming growth factor-β1 (TGF-β1) has been involved in epithelial mesenchymal transition. AngII mimics many profibrotic actions of TGF-β1. For these reasons, our aim was to investigate whether AngII could regulate the Notch/Jagged system in the kidney, and its potential role in AngII-induced responses. In cultured human tubular epithelial cells, TGF-β1, but not AngII, increased the Notch pathway-related gene expression, Jagged-1 synthesis, and caused nuclear translocation of the activated Notch. In podocytes and renal fibroblasts, AngII did not modulate the Notch pathway. In tubular epithelial cells, pharmacological Notch inhibition did not modify AngII-induced changes in epithelial mesenchymal markers, profibrotic factors and extracellular matrix proteins. Systemic infusion of AngII into rats for 2 weeks caused tubulointerstitial fibrosis, but did not upregulate renal expression of activated Notch-1 or Jagged-1, as observed in spontaneously hypertensive rats. Moreover, the Notch/Jagged system was not modulated by AngII type I receptor blockade in the model of unilateral ureteral obstruction in mice. These data clearly indicate that AngII does not regulate the Notch/Jagged signaling system in the kidney, in vivo and in vitro. Our findings showing that the Notch pathway is not involved in AngII-induced fibrosis could provide important information to understand the complex role of Notch system in the regulation of renal regeneration vs damage progression.</description><subject>Activation</subject><subject>Angiotensin</subject><subject>Angiotensin II</subject><subject>Angiotensin II - administration & dosage</subject><subject>Angiotensin II - toxicity</subject><subject>Angiotensins</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biology</subject><subject>Bone morphogenetic proteins</subject><subject>Calcium-Binding Proteins - genetics</subject><subject>Calcium-Binding Proteins - metabolism</subject><subject>Cell Line</subject><subject>Cellular biology</subject><subject>Development and progression</subject><subject>Diabetes</subject><subject>Disease Models, Animal</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - drug effects</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelial-Mesenchymal Transition - drug effects</subject><subject>Epithelial-Mesenchymal Transition - genetics</subject><subject>Extracellular matrix</subject><subject>Fibroblasts</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - metabolism</subject><subject>Fibrosis</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Genes</subject><subject>Human behavior</subject><subject>Humans</subject><subject>Hydronephrosis - genetics</subject><subject>Hydronephrosis - metabolism</subject><subject>Hypertension</subject><subject>Hypertension - chemically induced</subject><subject>Hypertension - genetics</subject><subject>Hypertension - metabolism</subject><subject>Intercellular Signaling Peptides and Proteins - genetics</subject><subject>Intercellular Signaling Peptides and Proteins - metabolism</subject><subject>Jagged-1 Protein</subject><subject>Kidney - drug effects</subject><subject>Kidney - metabolism</subject><subject>Kidney - pathology</subject><subject>Kidney diseases</subject><subject>Kidney Tubules - drug effects</subject><subject>Kidney Tubules - metabolism</subject><subject>Kidneys</subject><subject>Laboratories</subject><subject>Ligands</subject><subject>Male</subject><subject>Medicine</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Mesenchyme</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Nephrology</subject><subject>Notch protein</subject><subject>Notch1 protein</subject><subject>Nuclear transport</subject><subject>Pharmacology</subject><subject>Podocytes - drug effects</subject><subject>Podocytes - metabolism</subject><subject>Proteins</subject><subject>Rats</subject><subject>Receptor, Angiotensin, Type 1 - metabolism</subject><subject>Receptors, Notch - genetics</subject><subject>Receptors, Notch - metabolism</subject><subject>Regeneration</subject><subject>Rodents</subject><subject>Serrate-Jagged Proteins</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Smooth muscle</subject><subject>Stem cells</subject><subject>Transforming Growth Factor beta1 - biosynthesis</subject><subject>Transforming Growth Factor beta1 - pharmacology</subject><subject>Transforming growth factor-b1</subject><subject>Transforming growth factors</subject><subject>Translocation</subject><subject>Vascular endothelial growth factor</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkluL1DAYhoso7rr6D0QLguDFjDm2zY0wLB4Kiwse9jakadJm6CQ1SVfn35txussUFCSQhOT53ny8ebPsOQRriEv4dusmb8WwHp1VawAIIAw8yM4hw2hVIIAfnuzPsichbAGguCqKx9kZQiVDmMLz7GZjO-OissHYvK5z6Wz0ppmiCnl0uVfpiVybxrtgQm5sq0aVJhuHfe50_tlF2eejiP1Psc-FjOZWROPs0-yRFkNQz-b1Ivv-4f23y0-rq-uP9eXmaiVLWsVVRaGGWpZN0QqSehNKFYBoVEFJQCUlaggCUlDKsBSMUU2YLmiBCq1oS0iJL7KXR91xcIHPlgQOMaIEF5CQRNRHonViy0dvdsLvuROG_zlwvuPCRyMHxZGgTakwqbCgRCHNUFvollHEWlBCIpPWu_m1qdmpViYbvBgWossba3reuVuOMUPJ7yTwahbw7sekQvxHyzPVidSVsdolMbkzQfINKUsIMa1gotZ_odJo1c6kb1TapPNFwZtFweGr1a_YiSkEXn_98v_s9c2SfX3C9koMsQ9umA45CEuQHEGZ0hS80vfOQcAPmb5zgx8yzedMp7IXp67fF92FGP8G8V_xjg</recordid><startdate>20120709</startdate><enddate>20120709</enddate><creator>Lavoz, Carolina</creator><creator>Rodrigues-Diez, Raquel</creator><creator>Benito-Martin, Alberto</creator><creator>Rayego-Mateos, Sandra</creator><creator>Rodrigues-Diez, Raúl R</creator><creator>Alique, Matilde</creator><creator>Ortiz, Alberto</creator><creator>Mezzano, Sergio</creator><creator>Egido, Jesús</creator><creator>Ruiz-Ortega, Marta</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20120709</creationdate><title>Angiotensin II contributes to renal fibrosis independently of Notch pathway activation</title><author>Lavoz, Carolina ; Rodrigues-Diez, Raquel ; Benito-Martin, Alberto ; Rayego-Mateos, Sandra ; Rodrigues-Diez, Raúl R ; Alique, Matilde ; Ortiz, Alberto ; Mezzano, Sergio ; Egido, Jesús ; Ruiz-Ortega, Marta</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-851f1fc7b6da4386aee604f281c408cc2b420ca5593ca995f49f65626fe5d4473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Activation</topic><topic>Angiotensin</topic><topic>Angiotensin II</topic><topic>Angiotensin II - administration & dosage</topic><topic>Angiotensin II - toxicity</topic><topic>Angiotensins</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biology</topic><topic>Bone morphogenetic proteins</topic><topic>Calcium-Binding Proteins - genetics</topic><topic>Calcium-Binding Proteins - metabolism</topic><topic>Cell Line</topic><topic>Cellular biology</topic><topic>Development and progression</topic><topic>Diabetes</topic><topic>Disease Models, Animal</topic><topic>Epithelial cells</topic><topic>Epithelial Cells - drug effects</topic><topic>Epithelial Cells - metabolism</topic><topic>Epithelial-Mesenchymal Transition - drug effects</topic><topic>Epithelial-Mesenchymal Transition - genetics</topic><topic>Extracellular matrix</topic><topic>Fibroblasts</topic><topic>Fibroblasts - drug effects</topic><topic>Fibroblasts - metabolism</topic><topic>Fibrosis</topic><topic>Gene expression</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Genes</topic><topic>Human behavior</topic><topic>Humans</topic><topic>Hydronephrosis - genetics</topic><topic>Hydronephrosis - metabolism</topic><topic>Hypertension</topic><topic>Hypertension - chemically induced</topic><topic>Hypertension - genetics</topic><topic>Hypertension - metabolism</topic><topic>Intercellular Signaling Peptides and Proteins - genetics</topic><topic>Intercellular Signaling Peptides and Proteins - metabolism</topic><topic>Jagged-1 Protein</topic><topic>Kidney - drug effects</topic><topic>Kidney - metabolism</topic><topic>Kidney - pathology</topic><topic>Kidney diseases</topic><topic>Kidney Tubules - drug effects</topic><topic>Kidney Tubules - metabolism</topic><topic>Kidneys</topic><topic>Laboratories</topic><topic>Ligands</topic><topic>Male</topic><topic>Medicine</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Mesenchyme</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Nephrology</topic><topic>Notch protein</topic><topic>Notch1 protein</topic><topic>Nuclear transport</topic><topic>Pharmacology</topic><topic>Podocytes - drug effects</topic><topic>Podocytes - metabolism</topic><topic>Proteins</topic><topic>Rats</topic><topic>Receptor, Angiotensin, Type 1 - metabolism</topic><topic>Receptors, Notch - genetics</topic><topic>Receptors, Notch - metabolism</topic><topic>Regeneration</topic><topic>Rodents</topic><topic>Serrate-Jagged Proteins</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Smooth muscle</topic><topic>Stem cells</topic><topic>Transforming Growth Factor beta1 - biosynthesis</topic><topic>Transforming Growth Factor beta1 - pharmacology</topic><topic>Transforming growth factor-b1</topic><topic>Transforming growth factors</topic><topic>Translocation</topic><topic>Vascular endothelial growth factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lavoz, Carolina</creatorcontrib><creatorcontrib>Rodrigues-Diez, Raquel</creatorcontrib><creatorcontrib>Benito-Martin, Alberto</creatorcontrib><creatorcontrib>Rayego-Mateos, Sandra</creatorcontrib><creatorcontrib>Rodrigues-Diez, Raúl R</creatorcontrib><creatorcontrib>Alique, Matilde</creatorcontrib><creatorcontrib>Ortiz, Alberto</creatorcontrib><creatorcontrib>Mezzano, Sergio</creatorcontrib><creatorcontrib>Egido, Jesús</creatorcontrib><creatorcontrib>Ruiz-Ortega, Marta</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lavoz, Carolina</au><au>Rodrigues-Diez, Raquel</au><au>Benito-Martin, Alberto</au><au>Rayego-Mateos, Sandra</au><au>Rodrigues-Diez, Raúl R</au><au>Alique, Matilde</au><au>Ortiz, Alberto</au><au>Mezzano, Sergio</au><au>Egido, Jesús</au><au>Ruiz-Ortega, Marta</au><au>Chatziantoniou, Christos</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Angiotensin II contributes to renal fibrosis independently of Notch pathway activation</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-07-09</date><risdate>2012</risdate><volume>7</volume><issue>7</issue><spage>e40490</spage><pages>e40490-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Recent studies have described that the Notch signaling pathway is activated in a wide range of renal diseases. Angiotensin II (AngII) plays a key role in the progression of kidney diseases. AngII contributes to renal fibrosis by upregulation of profibrotic factors, induction of epithelial mesenchymal transition and accumulation of extracellular matrix proteins. In cultured human tubular epithelial cells the Notch activation by transforming growth factor-β1 (TGF-β1) has been involved in epithelial mesenchymal transition. AngII mimics many profibrotic actions of TGF-β1. For these reasons, our aim was to investigate whether AngII could regulate the Notch/Jagged system in the kidney, and its potential role in AngII-induced responses. In cultured human tubular epithelial cells, TGF-β1, but not AngII, increased the Notch pathway-related gene expression, Jagged-1 synthesis, and caused nuclear translocation of the activated Notch. In podocytes and renal fibroblasts, AngII did not modulate the Notch pathway. In tubular epithelial cells, pharmacological Notch inhibition did not modify AngII-induced changes in epithelial mesenchymal markers, profibrotic factors and extracellular matrix proteins. Systemic infusion of AngII into rats for 2 weeks caused tubulointerstitial fibrosis, but did not upregulate renal expression of activated Notch-1 or Jagged-1, as observed in spontaneously hypertensive rats. Moreover, the Notch/Jagged system was not modulated by AngII type I receptor blockade in the model of unilateral ureteral obstruction in mice. These data clearly indicate that AngII does not regulate the Notch/Jagged signaling system in the kidney, in vivo and in vitro. Our findings showing that the Notch pathway is not involved in AngII-induced fibrosis could provide important information to understand the complex role of Notch system in the regulation of renal regeneration vs damage progression.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22792351</pmid><doi>10.1371/journal.pone.0040490</doi><tpages>e40490</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-07, Vol.7 (7), p.e40490 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1325436144 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Activation Angiotensin Angiotensin II Angiotensin II - administration & dosage Angiotensin II - toxicity Angiotensins Animals Apoptosis Biology Bone morphogenetic proteins Calcium-Binding Proteins - genetics Calcium-Binding Proteins - metabolism Cell Line Cellular biology Development and progression Diabetes Disease Models, Animal Epithelial cells Epithelial Cells - drug effects Epithelial Cells - metabolism Epithelial-Mesenchymal Transition - drug effects Epithelial-Mesenchymal Transition - genetics Extracellular matrix Fibroblasts Fibroblasts - drug effects Fibroblasts - metabolism Fibrosis Gene expression Gene Expression Regulation - drug effects Genes Human behavior Humans Hydronephrosis - genetics Hydronephrosis - metabolism Hypertension Hypertension - chemically induced Hypertension - genetics Hypertension - metabolism Intercellular Signaling Peptides and Proteins - genetics Intercellular Signaling Peptides and Proteins - metabolism Jagged-1 Protein Kidney - drug effects Kidney - metabolism Kidney - pathology Kidney diseases Kidney Tubules - drug effects Kidney Tubules - metabolism Kidneys Laboratories Ligands Male Medicine Membrane Proteins - genetics Membrane Proteins - metabolism Mesenchyme Mice Mice, Inbred C57BL Nephrology Notch protein Notch1 protein Nuclear transport Pharmacology Podocytes - drug effects Podocytes - metabolism Proteins Rats Receptor, Angiotensin, Type 1 - metabolism Receptors, Notch - genetics Receptors, Notch - metabolism Regeneration Rodents Serrate-Jagged Proteins Signal Transduction Signaling Smooth muscle Stem cells Transforming Growth Factor beta1 - biosynthesis Transforming Growth Factor beta1 - pharmacology Transforming growth factor-b1 Transforming growth factors Translocation Vascular endothelial growth factor |
| title | Angiotensin II contributes to renal fibrosis independently of Notch pathway activation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T23%3A23%3A03IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Angiotensin%20II%20contributes%20to%20renal%20fibrosis%20independently%20of%20Notch%20pathway%20activation&rft.jtitle=PloS%20one&rft.au=Lavoz,%20Carolina&rft.date=2012-07-09&rft.volume=7&rft.issue=7&rft.spage=e40490&rft.pages=e40490-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0040490&rft_dat=%3Cgale_plos_%3EA477113581%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1325436144&rft_id=info:pmid/22792351&rft_galeid=A477113581&rft_doaj_id=oai_doaj_org_article_2a5b7e3483a54e2f92d6fd9529d0714c&rfr_iscdi=true |