Hyaluronan is apically secreted and expressed by proliferating or regenerating renal tubular cells
Hyaluronan is apically secreted and expressed by proliferating or regenerating renal tubular cells. Hyaluronan has diverse biologic functions in the body, varying from structural tasks to cell stress-induced CD44-mediated activation of intracellular signaling pathways. Hyaluronan biology is relative...
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| description | Hyaluronan is apically secreted and expressed by proliferating or regenerating renal tubular cells.
Hyaluronan has diverse biologic functions in the body, varying from structural tasks to cell stress-induced CD44-mediated activation of intracellular signaling pathways. Hyaluronan biology is relatively unexplored in the kidney. Previously, we identified hyaluronan as binding molecule for crystals in the renal tubules. Crystal retention is a crucial early event in the etiology of kidney stones. The present study was performed to determine the polarized distribution of hyaluronan and CD44 by renal tubular cells.
Madin-Darby canine kidney (MDCK) strain I and primary cultures of human renal tubular cells were grown on permeable supports in a two-compartment culture system. Studies were performed during growth and after scrape-injury. Metabolic labeling studies and an enzyme-linked hyaluronan -binding assay were used to measure the molecular mass and the amount of secreted hyaluronan in apical and basal medium. Confocal microscopy was applied to detect membrane hyaluronan and CD44. Hyaluronan synthase (HAS) mRNA expression was studied with reverse transcriptase-polymerase chain reaction (RT-PCR). The in vitro expression profile of hyaluronan was compared with that in biopsies of transplanted human kidneys with acute tubular necrosis.
Proliferating cells produced more hyaluronan (Mr > 106 Da) than growth-inhibited cells in intact monolayers and up to 85% was targeted to the apical compartment, which was accompanied by increased HAS2 mRNA expression and slightly decreased HAS3 mRNA, while HAS1 mRNA remained undetectable. Hyaluronan and CD44 were exclusively expressed at the apical surface of proliferating/regenerating cells. After (re)establishment of tight junctions, hyaluronan was no longer detectable while CD44 was targeted to basolateral membrane domains. In vivo in inflamed human kidneys hyaluronan was abundantly expressed in the cortical tubulointerstitial space as well as at the luminal surface of regenerating renal tubular cells.
These results demonstrate that the production of hyaluronan by renal tubular cells is activated during proliferation and in response to mechanical injury and that hyaluronan and CD44 expression is highly polarized. The targeted delivery of hyaluronan to the apical compartment suggests that hyaluronan produced by renal tubular cells supports proliferation/regeneration in the renal tubules, but that it does not contribute to hyaluro |
| doi_str_mv | 10.1111/j.1523-1755.2005.00382.x |
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Hyaluronan has diverse biologic functions in the body, varying from structural tasks to cell stress-induced CD44-mediated activation of intracellular signaling pathways. Hyaluronan biology is relatively unexplored in the kidney. Previously, we identified hyaluronan as binding molecule for crystals in the renal tubules. Crystal retention is a crucial early event in the etiology of kidney stones. The present study was performed to determine the polarized distribution of hyaluronan and CD44 by renal tubular cells.
Madin-Darby canine kidney (MDCK) strain I and primary cultures of human renal tubular cells were grown on permeable supports in a two-compartment culture system. Studies were performed during growth and after scrape-injury. Metabolic labeling studies and an enzyme-linked hyaluronan -binding assay were used to measure the molecular mass and the amount of secreted hyaluronan in apical and basal medium. Confocal microscopy was applied to detect membrane hyaluronan and CD44. Hyaluronan synthase (HAS) mRNA expression was studied with reverse transcriptase-polymerase chain reaction (RT-PCR). The in vitro expression profile of hyaluronan was compared with that in biopsies of transplanted human kidneys with acute tubular necrosis.
Proliferating cells produced more hyaluronan (Mr > 106 Da) than growth-inhibited cells in intact monolayers and up to 85% was targeted to the apical compartment, which was accompanied by increased HAS2 mRNA expression and slightly decreased HAS3 mRNA, while HAS1 mRNA remained undetectable. Hyaluronan and CD44 were exclusively expressed at the apical surface of proliferating/regenerating cells. After (re)establishment of tight junctions, hyaluronan was no longer detectable while CD44 was targeted to basolateral membrane domains. In vivo in inflamed human kidneys hyaluronan was abundantly expressed in the cortical tubulointerstitial space as well as at the luminal surface of regenerating renal tubular cells.
These results demonstrate that the production of hyaluronan by renal tubular cells is activated during proliferation and in response to mechanical injury and that hyaluronan and CD44 expression is highly polarized. The targeted delivery of hyaluronan to the apical compartment suggests that hyaluronan produced by renal tubular cells supports proliferation/regeneration in the renal tubules, but that it does not contribute to hyaluronan accumulation in the renal interstitium. These data further support the concept that mitogen/stress-induced hyaluronan deposition in the renal tubules increases the risk for crystal retention and stone formation.</description><identifier>ISSN: 0085-2538</identifier><identifier>EISSN: 1523-1755</identifier><identifier>DOI: 10.1111/j.1523-1755.2005.00382.x</identifier><identifier>PMID: 15954897</identifier><identifier>CODEN: KDYIA5</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Animals ; Antimetabolites ; Base Sequence ; Biological and medical sciences ; Bromodeoxyuridine ; CD44 ; Cell Division - physiology ; Cell Line ; Cell Polarity - physiology ; Dogs ; Gene Expression Regulation, Enzymologic ; Glucuronosyltransferase - genetics ; Humans ; hyaluronan ; Hyaluronan Receptors - metabolism ; Hyaluronan Synthases ; Hyaluronic Acid - biosynthesis ; Hyaluronic Acid - metabolism ; Hyaluronic Acid - secretion ; Kidney Tubular Necrosis, Acute - metabolism ; Kidney Tubular Necrosis, Acute - physiopathology ; Kidney Tubules - cytology ; Kidney Tubules - metabolism ; Medical sciences ; Microscopy, Confocal ; Molecular Sequence Data ; Nephrology. Urinary tract diseases ; polarity ; Regeneration - physiology ; renal stone disease ; renal tubular cells ; Reverse Transcriptase Polymerase Chain Reaction ; Tritium</subject><ispartof>Kidney international, 2005-07, Vol.68 (1), p.71-83</ispartof><rights>2005 International Society of Nephrology</rights><rights>2005 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Jul 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c567t-92ff9efd2a6b9a0484260861c4fdfb54d82f36d924ab49942e2b79126aea7b593</citedby><cites>FETCH-LOGICAL-c567t-92ff9efd2a6b9a0484260861c4fdfb54d82f36d924ab49942e2b79126aea7b593</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/210169152?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,64385,64389,72469</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16903691$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15954897$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Asselman, Marino</creatorcontrib><creatorcontrib>Verhulst, Anja</creatorcontrib><creatorcontrib>Van Ballegooijen, Eddy S.</creatorcontrib><creatorcontrib>Bangma, Chris H.</creatorcontrib><creatorcontrib>Verkoelen, Carl F.</creatorcontrib><creatorcontrib>De Broe, Marc E.</creatorcontrib><title>Hyaluronan is apically secreted and expressed by proliferating or regenerating renal tubular cells</title><title>Kidney international</title><addtitle>Kidney Int</addtitle><description>Hyaluronan is apically secreted and expressed by proliferating or regenerating renal tubular cells.
Hyaluronan has diverse biologic functions in the body, varying from structural tasks to cell stress-induced CD44-mediated activation of intracellular signaling pathways. Hyaluronan biology is relatively unexplored in the kidney. Previously, we identified hyaluronan as binding molecule for crystals in the renal tubules. Crystal retention is a crucial early event in the etiology of kidney stones. The present study was performed to determine the polarized distribution of hyaluronan and CD44 by renal tubular cells.
Madin-Darby canine kidney (MDCK) strain I and primary cultures of human renal tubular cells were grown on permeable supports in a two-compartment culture system. Studies were performed during growth and after scrape-injury. Metabolic labeling studies and an enzyme-linked hyaluronan -binding assay were used to measure the molecular mass and the amount of secreted hyaluronan in apical and basal medium. Confocal microscopy was applied to detect membrane hyaluronan and CD44. Hyaluronan synthase (HAS) mRNA expression was studied with reverse transcriptase-polymerase chain reaction (RT-PCR). The in vitro expression profile of hyaluronan was compared with that in biopsies of transplanted human kidneys with acute tubular necrosis.
Proliferating cells produced more hyaluronan (Mr > 106 Da) than growth-inhibited cells in intact monolayers and up to 85% was targeted to the apical compartment, which was accompanied by increased HAS2 mRNA expression and slightly decreased HAS3 mRNA, while HAS1 mRNA remained undetectable. Hyaluronan and CD44 were exclusively expressed at the apical surface of proliferating/regenerating cells. After (re)establishment of tight junctions, hyaluronan was no longer detectable while CD44 was targeted to basolateral membrane domains. In vivo in inflamed human kidneys hyaluronan was abundantly expressed in the cortical tubulointerstitial space as well as at the luminal surface of regenerating renal tubular cells.
These results demonstrate that the production of hyaluronan by renal tubular cells is activated during proliferation and in response to mechanical injury and that hyaluronan and CD44 expression is highly polarized. The targeted delivery of hyaluronan to the apical compartment suggests that hyaluronan produced by renal tubular cells supports proliferation/regeneration in the renal tubules, but that it does not contribute to hyaluronan accumulation in the renal interstitium. These data further support the concept that mitogen/stress-induced hyaluronan deposition in the renal tubules increases the risk for crystal retention and stone formation.</description><subject>Animals</subject><subject>Antimetabolites</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Bromodeoxyuridine</subject><subject>CD44</subject><subject>Cell Division - physiology</subject><subject>Cell Line</subject><subject>Cell Polarity - physiology</subject><subject>Dogs</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Glucuronosyltransferase - genetics</subject><subject>Humans</subject><subject>hyaluronan</subject><subject>Hyaluronan Receptors - metabolism</subject><subject>Hyaluronan Synthases</subject><subject>Hyaluronic Acid - biosynthesis</subject><subject>Hyaluronic Acid - metabolism</subject><subject>Hyaluronic Acid - secretion</subject><subject>Kidney Tubular Necrosis, Acute - metabolism</subject><subject>Kidney Tubular Necrosis, Acute - physiopathology</subject><subject>Kidney Tubules - cytology</subject><subject>Kidney Tubules - metabolism</subject><subject>Medical sciences</subject><subject>Microscopy, Confocal</subject><subject>Molecular Sequence Data</subject><subject>Nephrology. Urinary tract diseases</subject><subject>polarity</subject><subject>Regeneration - physiology</subject><subject>renal stone disease</subject><subject>renal tubular cells</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Tritium</subject><issn>0085-2538</issn><issn>1523-1755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqFkNFuFCEUhomxsevqI2iIiZczAgPMcKmNWpMm3rTXBJhDw4YyK8yY3bcv013bS7khJ_93Tv58CGFKWlrfl11LBesa2gvRMkJES0g3sPbwCm2eg9doQ8ggGia64RK9LWVH6qw68gZdUqEEH1S_Qfb6aOKSp2QSDgWbfXAmxiMu4DLMMGKTRgyHfYZS6mSPeJ-nGDxkM4d0j6eMM9xD-jdnSCbiebFLNBk7iLG8QxfexALvz_8W3f34fnt13dz8_vnr6utN44Ts50Yx7xX4kRlplSF84EySQVLH_eit4OPAfCdHxbixXCnOgNleUSYNmN4K1W3Rp9Pd2vDPAmXWu2nJtU7RjBIq1apmi4YT5PJUSgav9zk8mHzUlOjVrd7pldOrQr261U9u9aGufjzfX-wDjC-LZ5kV-HwGTKkWfTbJhfLCSUW62qJyH05cMvOS4RngXEkiZc2_nXKotv4GyLq4AMnBGDK4WY9T-H_bR2UIosY</recordid><startdate>20050701</startdate><enddate>20050701</enddate><creator>Asselman, Marino</creator><creator>Verhulst, Anja</creator><creator>Van Ballegooijen, Eddy S.</creator><creator>Bangma, Chris H.</creator><creator>Verkoelen, Carl F.</creator><creator>De Broe, Marc E.</creator><general>Elsevier Inc</general><general>Nature Publishing</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><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>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope></search><sort><creationdate>20050701</creationdate><title>Hyaluronan is apically secreted and expressed by proliferating or regenerating renal tubular cells</title><author>Asselman, Marino ; Verhulst, Anja ; Van Ballegooijen, Eddy S. ; Bangma, Chris H. ; Verkoelen, Carl F. ; De Broe, Marc E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c567t-92ff9efd2a6b9a0484260861c4fdfb54d82f36d924ab49942e2b79126aea7b593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Antimetabolites</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Bromodeoxyuridine</topic><topic>CD44</topic><topic>Cell Division - physiology</topic><topic>Cell Line</topic><topic>Cell Polarity - physiology</topic><topic>Dogs</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Glucuronosyltransferase - genetics</topic><topic>Humans</topic><topic>hyaluronan</topic><topic>Hyaluronan Receptors - metabolism</topic><topic>Hyaluronan Synthases</topic><topic>Hyaluronic Acid - biosynthesis</topic><topic>Hyaluronic Acid - metabolism</topic><topic>Hyaluronic Acid - secretion</topic><topic>Kidney Tubular Necrosis, Acute - metabolism</topic><topic>Kidney Tubular Necrosis, Acute - physiopathology</topic><topic>Kidney Tubules - cytology</topic><topic>Kidney Tubules - metabolism</topic><topic>Medical sciences</topic><topic>Microscopy, Confocal</topic><topic>Molecular Sequence Data</topic><topic>Nephrology. Urinary tract diseases</topic><topic>polarity</topic><topic>Regeneration - physiology</topic><topic>renal stone disease</topic><topic>renal tubular cells</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Tritium</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Asselman, Marino</creatorcontrib><creatorcontrib>Verhulst, Anja</creatorcontrib><creatorcontrib>Van Ballegooijen, Eddy S.</creatorcontrib><creatorcontrib>Bangma, Chris H.</creatorcontrib><creatorcontrib>Verkoelen, Carl F.</creatorcontrib><creatorcontrib>De Broe, Marc E.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</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>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><jtitle>Kidney international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Asselman, Marino</au><au>Verhulst, Anja</au><au>Van Ballegooijen, Eddy S.</au><au>Bangma, Chris H.</au><au>Verkoelen, Carl F.</au><au>De Broe, Marc E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hyaluronan is apically secreted and expressed by proliferating or regenerating renal tubular cells</atitle><jtitle>Kidney international</jtitle><addtitle>Kidney Int</addtitle><date>2005-07-01</date><risdate>2005</risdate><volume>68</volume><issue>1</issue><spage>71</spage><epage>83</epage><pages>71-83</pages><issn>0085-2538</issn><eissn>1523-1755</eissn><coden>KDYIA5</coden><abstract>Hyaluronan is apically secreted and expressed by proliferating or regenerating renal tubular cells.
Hyaluronan has diverse biologic functions in the body, varying from structural tasks to cell stress-induced CD44-mediated activation of intracellular signaling pathways. Hyaluronan biology is relatively unexplored in the kidney. Previously, we identified hyaluronan as binding molecule for crystals in the renal tubules. Crystal retention is a crucial early event in the etiology of kidney stones. The present study was performed to determine the polarized distribution of hyaluronan and CD44 by renal tubular cells.
Madin-Darby canine kidney (MDCK) strain I and primary cultures of human renal tubular cells were grown on permeable supports in a two-compartment culture system. Studies were performed during growth and after scrape-injury. Metabolic labeling studies and an enzyme-linked hyaluronan -binding assay were used to measure the molecular mass and the amount of secreted hyaluronan in apical and basal medium. Confocal microscopy was applied to detect membrane hyaluronan and CD44. Hyaluronan synthase (HAS) mRNA expression was studied with reverse transcriptase-polymerase chain reaction (RT-PCR). The in vitro expression profile of hyaluronan was compared with that in biopsies of transplanted human kidneys with acute tubular necrosis.
Proliferating cells produced more hyaluronan (Mr > 106 Da) than growth-inhibited cells in intact monolayers and up to 85% was targeted to the apical compartment, which was accompanied by increased HAS2 mRNA expression and slightly decreased HAS3 mRNA, while HAS1 mRNA remained undetectable. Hyaluronan and CD44 were exclusively expressed at the apical surface of proliferating/regenerating cells. After (re)establishment of tight junctions, hyaluronan was no longer detectable while CD44 was targeted to basolateral membrane domains. In vivo in inflamed human kidneys hyaluronan was abundantly expressed in the cortical tubulointerstitial space as well as at the luminal surface of regenerating renal tubular cells.
These results demonstrate that the production of hyaluronan by renal tubular cells is activated during proliferation and in response to mechanical injury and that hyaluronan and CD44 expression is highly polarized. The targeted delivery of hyaluronan to the apical compartment suggests that hyaluronan produced by renal tubular cells supports proliferation/regeneration in the renal tubules, but that it does not contribute to hyaluronan accumulation in the renal interstitium. These data further support the concept that mitogen/stress-induced hyaluronan deposition in the renal tubules increases the risk for crystal retention and stone formation.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>15954897</pmid><doi>10.1111/j.1523-1755.2005.00382.x</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; ProQuest Central UK/Ireland; Alma/SFX Local Collection |
| subjects | Animals Antimetabolites Base Sequence Biological and medical sciences Bromodeoxyuridine CD44 Cell Division - physiology Cell Line Cell Polarity - physiology Dogs Gene Expression Regulation, Enzymologic Glucuronosyltransferase - genetics Humans hyaluronan Hyaluronan Receptors - metabolism Hyaluronan Synthases Hyaluronic Acid - biosynthesis Hyaluronic Acid - metabolism Hyaluronic Acid - secretion Kidney Tubular Necrosis, Acute - metabolism Kidney Tubular Necrosis, Acute - physiopathology Kidney Tubules - cytology Kidney Tubules - metabolism Medical sciences Microscopy, Confocal Molecular Sequence Data Nephrology. Urinary tract diseases polarity Regeneration - physiology renal stone disease renal tubular cells Reverse Transcriptase Polymerase Chain Reaction Tritium |
| title | Hyaluronan is apically secreted and expressed by proliferating or regenerating renal tubular cells |
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