The Accumulation of VEGFA in the Glomerular Basement Membrane and Its Relationship with Podocyte Injury and Proteinuria in Alport Syndrome
The pathogenesis of proteinuria in Alport syndrome (AS) remains unclear. Vascular endothelial growth factor A (VEGFA) is a key regulator of the glomerular filtration barrier (GFB). This study explored the expression of VEGFA in the glomeruli and its accumulation in the glomerular basement membrane (...
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| description | The pathogenesis of proteinuria in Alport syndrome (AS) remains unclear. Vascular endothelial growth factor A (VEGFA) is a key regulator of the glomerular filtration barrier (GFB). This study explored the expression of VEGFA in the glomeruli and its accumulation in the glomerular basement membrane (GBM) and their relationship with podocyte injury and proteinuria in Alport syndrome (AS). Clinical data and renal tissues of control patients (11 cases) and AS patients (25 cases) were included. AS patients were further divided into 2 groups according to the quantities of their urinary protein: mild to moderate proteinuria group (proteinuria |
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Vascular endothelial growth factor A (VEGFA) is a key regulator of the glomerular filtration barrier (GFB). This study explored the expression of VEGFA in the glomeruli and its accumulation in the glomerular basement membrane (GBM) and their relationship with podocyte injury and proteinuria in Alport syndrome (AS). Clinical data and renal tissues of control patients (11 cases) and AS patients (25 cases) were included. AS patients were further divided into 2 groups according to the quantities of their urinary protein: mild to moderate proteinuria group (proteinuria <50 mg/kg/d, 15 cases) and heavy proteinuria group (proteinuria ≥50 mg/kg/d, 10 cases). The expression and distribution of VEGFA and VEGF receptor 2 (VEGFR2) in the GFB, the phosphorylation of VEGFR2 (p-VEGFR2) and nephrin (p-nephrin), and the expression of synaptopodin and nephrin in the glomeruli were detected by immune electron microscopy and/or immunofluorescence, and their relationships to proteinuria in AS patients were analyzed. The accumulation of VEGFA in the GBM was increased in AS patients. The expression of VEGFA and the levels of p-VEGFR2 and p-nephrin in glomeruli were increased and were positively correlated with the degree of proteinuria in AS patients. The expression of synaptopodin and nephrin were decreased and were negatively correlated with the degree of proteinuria in AS patients. The over expressed VEGFA in the glomeruli and its accumulation in the GBM may activate the VEGFA-VEGFR2 and nephrin signaling pathways and lead to podocyte injury and occurrence of proteinuria in AS.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0135648</identifier><identifier>PMID: 26274923</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Accumulation ; Adolescent ; Alport syndrome ; Analysis ; Basement membranes ; Biomarkers - metabolism ; Case-Control Studies ; Cell adhesion & migration ; Child ; Child, Preschool ; Congenital diseases ; Electron microscopy ; Female ; Glomerular Basement Membrane - metabolism ; Glomerular Basement Membrane - pathology ; Hospitals ; Humans ; Immunofluorescence ; Immunoglobulins ; Injuries ; Kidney diseases ; Male ; Membrane Proteins - metabolism ; Microfilament Proteins - metabolism ; Microscopy ; Nephritis, Hereditary - metabolism ; Nephritis, Hereditary - pathology ; Nephritis, Hereditary - physiopathology ; Pathogenesis ; Patients ; Pediatrics ; Phosphorylation ; Podocytes - metabolism ; Podocytes - pathology ; Proteins ; Proteinuria ; Proteinuria - etiology ; Proteinuria - metabolism ; Rodents ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - metabolism ; Vascular Endothelial Growth Factor Receptor-2 - metabolism</subject><ispartof>PloS one, 2015-08, Vol.10 (8), p.e0135648-e0135648</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://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>2015 Wang et al 2015 Wang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-c62c933f2de3edbe4c206cb669745b95030b33bd39607ad660d226208602c4913</citedby><cites>FETCH-LOGICAL-c692t-c62c933f2de3edbe4c206cb669745b95030b33bd39607ad660d226208602c4913</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/PMC4537134/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537134/$$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/26274923$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Jia, Zhanjun</contributor><creatorcontrib>Wang, Haiyan</creatorcontrib><creatorcontrib>Yue, Zhihui</creatorcontrib><creatorcontrib>Wu, Jinlang</creatorcontrib><creatorcontrib>Liu, Ting</creatorcontrib><creatorcontrib>Mo, Ying</creatorcontrib><creatorcontrib>Jiang, Xiaoyun</creatorcontrib><creatorcontrib>Sun, Liangzhong</creatorcontrib><title>The Accumulation of VEGFA in the Glomerular Basement Membrane and Its Relationship with Podocyte Injury and Proteinuria in Alport Syndrome</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The pathogenesis of proteinuria in Alport syndrome (AS) remains unclear. Vascular endothelial growth factor A (VEGFA) is a key regulator of the glomerular filtration barrier (GFB). This study explored the expression of VEGFA in the glomeruli and its accumulation in the glomerular basement membrane (GBM) and their relationship with podocyte injury and proteinuria in Alport syndrome (AS). Clinical data and renal tissues of control patients (11 cases) and AS patients (25 cases) were included. AS patients were further divided into 2 groups according to the quantities of their urinary protein: mild to moderate proteinuria group (proteinuria <50 mg/kg/d, 15 cases) and heavy proteinuria group (proteinuria ≥50 mg/kg/d, 10 cases). The expression and distribution of VEGFA and VEGF receptor 2 (VEGFR2) in the GFB, the phosphorylation of VEGFR2 (p-VEGFR2) and nephrin (p-nephrin), and the expression of synaptopodin and nephrin in the glomeruli were detected by immune electron microscopy and/or immunofluorescence, and their relationships to proteinuria in AS patients were analyzed. The accumulation of VEGFA in the GBM was increased in AS patients. The expression of VEGFA and the levels of p-VEGFR2 and p-nephrin in glomeruli were increased and were positively correlated with the degree of proteinuria in AS patients. The expression of synaptopodin and nephrin were decreased and were negatively correlated with the degree of proteinuria in AS patients. The over expressed VEGFA in the glomeruli and its accumulation in the GBM may activate the VEGFA-VEGFR2 and nephrin signaling pathways and lead to podocyte injury and occurrence of proteinuria in AS.</description><subject>Accumulation</subject><subject>Adolescent</subject><subject>Alport syndrome</subject><subject>Analysis</subject><subject>Basement membranes</subject><subject>Biomarkers - metabolism</subject><subject>Case-Control Studies</subject><subject>Cell adhesion & migration</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Congenital diseases</subject><subject>Electron microscopy</subject><subject>Female</subject><subject>Glomerular Basement Membrane - metabolism</subject><subject>Glomerular Basement Membrane - pathology</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunofluorescence</subject><subject>Immunoglobulins</subject><subject>Injuries</subject><subject>Kidney diseases</subject><subject>Male</subject><subject>Membrane Proteins - metabolism</subject><subject>Microfilament Proteins - metabolism</subject><subject>Microscopy</subject><subject>Nephritis, Hereditary - metabolism</subject><subject>Nephritis, Hereditary - pathology</subject><subject>Nephritis, Hereditary - physiopathology</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Phosphorylation</subject><subject>Podocytes - metabolism</subject><subject>Podocytes - pathology</subject><subject>Proteins</subject><subject>Proteinuria</subject><subject>Proteinuria - etiology</subject><subject>Proteinuria - metabolism</subject><subject>Rodents</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>Vascular Endothelial Growth Factor Receptor-2 - metabolism</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</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>eNqNk9Fu0zAUhiMEYmPwBggsISG4aHFsx0lukMq0lUpDm7axW8txnMaVYxfbAfoKPDVum00N2gWKlEQ-3_8fn2OfJHmdwmmK8_TTyvbOcD1dWyOnMMUZJcWT5DgtMZpQBPHTg_-j5IX3KwgzXFD6PDlCFOWkRPg4-XPbSjATou96zYOyBtgG3J3Nz2dAGRBicK5tJ12MOvCFe9lJE8A32VWOGwm4qcEieHAt92rfqjX4pUILrmxtxSZIsDCr3m125JWzQSrTO8W37jO9ti6Am42pXczxMnnWcO3lq-F7knw_P7s9_Tq5uJwvTmcXE0FLFOIbiRLjBtUSy7qSRCBIRUVpmZOsKjOIYYVxVeOSwpzXlMIaxXphQSESpEzxSfJ277vW1rOhjZ6lOSSQYohIJBZ7orZ8xdZOddxtmOWK7RasWzLughJasoxklDYFbKKS0FxUvKKlkBIVOWwaUUSvz0O2vupkLWL7HNcj03HEqJYt7U9GsnjKeLuZD4OBsz966QPrlBdS69h_2-_2ncEUFgWN6Lt_0MerG6gljwUo09iYV2xN2YygjKaUYByp6SNUfGrZKRHvXKPi-kjwcSSITJC_w5L33rPFzfX_s5d3Y_b9AdtKrkPrre53120Mkj0onPXeyeahySlk25G57wbbjgwbRibK3hwe0IPofkbwX4ljEKY</recordid><startdate>20150814</startdate><enddate>20150814</enddate><creator>Wang, Haiyan</creator><creator>Yue, Zhihui</creator><creator>Wu, Jinlang</creator><creator>Liu, Ting</creator><creator>Mo, Ying</creator><creator>Jiang, Xiaoyun</creator><creator>Sun, Liangzhong</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>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150814</creationdate><title>The Accumulation of VEGFA in the Glomerular Basement Membrane and Its Relationship with Podocyte Injury and Proteinuria in Alport Syndrome</title><author>Wang, Haiyan ; Yue, Zhihui ; Wu, Jinlang ; Liu, Ting ; Mo, Ying ; Jiang, Xiaoyun ; Sun, Liangzhong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-c62c933f2de3edbe4c206cb669745b95030b33bd39607ad660d226208602c4913</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Accumulation</topic><topic>Adolescent</topic><topic>Alport syndrome</topic><topic>Analysis</topic><topic>Basement membranes</topic><topic>Biomarkers - metabolism</topic><topic>Case-Control Studies</topic><topic>Cell adhesion & migration</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Congenital diseases</topic><topic>Electron microscopy</topic><topic>Female</topic><topic>Glomerular Basement Membrane - metabolism</topic><topic>Glomerular Basement Membrane - pathology</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Immunofluorescence</topic><topic>Immunoglobulins</topic><topic>Injuries</topic><topic>Kidney diseases</topic><topic>Male</topic><topic>Membrane Proteins - metabolism</topic><topic>Microfilament Proteins - metabolism</topic><topic>Microscopy</topic><topic>Nephritis, Hereditary - metabolism</topic><topic>Nephritis, Hereditary - pathology</topic><topic>Nephritis, Hereditary - physiopathology</topic><topic>Pathogenesis</topic><topic>Patients</topic><topic>Pediatrics</topic><topic>Phosphorylation</topic><topic>Podocytes - metabolism</topic><topic>Podocytes - pathology</topic><topic>Proteins</topic><topic>Proteinuria</topic><topic>Proteinuria - 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Academic</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>Wang, Haiyan</au><au>Yue, Zhihui</au><au>Wu, Jinlang</au><au>Liu, Ting</au><au>Mo, Ying</au><au>Jiang, Xiaoyun</au><au>Sun, Liangzhong</au><au>Jia, Zhanjun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Accumulation of VEGFA in the Glomerular Basement Membrane and Its Relationship with Podocyte Injury and Proteinuria in Alport Syndrome</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-08-14</date><risdate>2015</risdate><volume>10</volume><issue>8</issue><spage>e0135648</spage><epage>e0135648</epage><pages>e0135648-e0135648</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The pathogenesis of proteinuria in Alport syndrome (AS) remains unclear. Vascular endothelial growth factor A (VEGFA) is a key regulator of the glomerular filtration barrier (GFB). This study explored the expression of VEGFA in the glomeruli and its accumulation in the glomerular basement membrane (GBM) and their relationship with podocyte injury and proteinuria in Alport syndrome (AS). Clinical data and renal tissues of control patients (11 cases) and AS patients (25 cases) were included. AS patients were further divided into 2 groups according to the quantities of their urinary protein: mild to moderate proteinuria group (proteinuria <50 mg/kg/d, 15 cases) and heavy proteinuria group (proteinuria ≥50 mg/kg/d, 10 cases). The expression and distribution of VEGFA and VEGF receptor 2 (VEGFR2) in the GFB, the phosphorylation of VEGFR2 (p-VEGFR2) and nephrin (p-nephrin), and the expression of synaptopodin and nephrin in the glomeruli were detected by immune electron microscopy and/or immunofluorescence, and their relationships to proteinuria in AS patients were analyzed. The accumulation of VEGFA in the GBM was increased in AS patients. The expression of VEGFA and the levels of p-VEGFR2 and p-nephrin in glomeruli were increased and were positively correlated with the degree of proteinuria in AS patients. The expression of synaptopodin and nephrin were decreased and were negatively correlated with the degree of proteinuria in AS patients. The over expressed VEGFA in the glomeruli and its accumulation in the GBM may activate the VEGFA-VEGFR2 and nephrin signaling pathways and lead to podocyte injury and occurrence of proteinuria in AS.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26274923</pmid><doi>10.1371/journal.pone.0135648</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Accumulation Adolescent Alport syndrome Analysis Basement membranes Biomarkers - metabolism Case-Control Studies Cell adhesion & migration Child Child, Preschool Congenital diseases Electron microscopy Female Glomerular Basement Membrane - metabolism Glomerular Basement Membrane - pathology Hospitals Humans Immunofluorescence Immunoglobulins Injuries Kidney diseases Male Membrane Proteins - metabolism Microfilament Proteins - metabolism Microscopy Nephritis, Hereditary - metabolism Nephritis, Hereditary - pathology Nephritis, Hereditary - physiopathology Pathogenesis Patients Pediatrics Phosphorylation Podocytes - metabolism Podocytes - pathology Proteins Proteinuria Proteinuria - etiology Proteinuria - metabolism Rodents Vascular endothelial growth factor Vascular Endothelial Growth Factor A - metabolism Vascular Endothelial Growth Factor Receptor-2 - metabolism |
| title | The Accumulation of VEGFA in the Glomerular Basement Membrane and Its Relationship with Podocyte Injury and Proteinuria in Alport Syndrome |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T23%3A45%3A11IST&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=The%20Accumulation%20of%20VEGFA%20in%20the%20Glomerular%20Basement%20Membrane%20and%20Its%20Relationship%20with%20Podocyte%20Injury%20and%20Proteinuria%20in%20Alport%20Syndrome&rft.jtitle=PloS%20one&rft.au=Wang,%20Haiyan&rft.date=2015-08-14&rft.volume=10&rft.issue=8&rft.spage=e0135648&rft.epage=e0135648&rft.pages=e0135648-e0135648&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0135648&rft_dat=%3Cgale_plos_%3EA425616433%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=1704063024&rft_id=info:pmid/26274923&rft_galeid=A425616433&rft_doaj_id=oai_doaj_org_article_54566f80f630467cbab69cee2870ffc8&rfr_iscdi=true |