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Role of endothelial‐to‐mesenchymal transition induced by TGF‐β1 in transplant kidney interstitial fibrosis
Chronic allograft dysfunction (CAD) induced by kidney interstitial fibrosis is the main cause of allograft failure in kidney transplantation. Endothelial‐to‐mesenchymal transition (EndMT) may play an important role in kidney fibrosis. We, therefore, undertook this study to characterize the functions...
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| Published in: | Journal of cellular and molecular medicine 2017-10, Vol.21 (10), p.2359-2369 |
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| creator | Wang, Zijie Han, Zhijian Tao, Jun Wang, Jun Liu, Xuzhong Zhou, Wanli Xu, Zhen Zhao, Chunchun Wang, Zengjun Tan, Ruoyun Gu, Min |
| description | Chronic allograft dysfunction (CAD) induced by kidney interstitial fibrosis is the main cause of allograft failure in kidney transplantation. Endothelial‐to‐mesenchymal transition (EndMT) may play an important role in kidney fibrosis. We, therefore, undertook this study to characterize the functions and potential mechanism of EndMT in transplant kidney interstitial fibrosis. Proteins and mRNAs associated with EndMT were examined in human umbilical vein endothelial cells (HUVECs) treated with transforming growth factor‐beta1 (TGF‐β1) at different doses or at different intervals with western blotting, qRT‐PCR and ELISA assays. Cell motility and migration were evaluated with motility and migration assays. The mechanism of EndMT induced by TGF‐β1 was determined by western blotting analysis of factors involved in various canonical and non‐canonical pathways. In addition, human kidney tissues from control and CAD group were also examined for these proteins by HE, Masson's trichrome, immunohistochemical, indirect immunofluorescence double staining and western blotting assays. TGF‐β1 significantly promoted the development of EndMT in a time‐dependent and dose‐dependent manner and promoted the motility and migration ability of HUVECs. The TGF‐β/Smad and Akt/mTOR/p70S6K signalling pathways were found to be associated with the pathogenesis of EndMT induced by TGF‐β1, which was also proven in vivo by the analysis of specimens from the control and CAD groups. EndMT may promote transplant kidney interstitial fibrosis by targetting the TGF‐β/Smad and Akt/mTOR/p70S6K signalling pathways, and hence, result in the development of CAD in kidney transplant recipients. |
| doi_str_mv | 10.1111/jcmm.13157 |
| format | article |
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Endothelial‐to‐mesenchymal transition (EndMT) may play an important role in kidney fibrosis. We, therefore, undertook this study to characterize the functions and potential mechanism of EndMT in transplant kidney interstitial fibrosis. Proteins and mRNAs associated with EndMT were examined in human umbilical vein endothelial cells (HUVECs) treated with transforming growth factor‐beta1 (TGF‐β1) at different doses or at different intervals with western blotting, qRT‐PCR and ELISA assays. Cell motility and migration were evaluated with motility and migration assays. The mechanism of EndMT induced by TGF‐β1 was determined by western blotting analysis of factors involved in various canonical and non‐canonical pathways. In addition, human kidney tissues from control and CAD group were also examined for these proteins by HE, Masson's trichrome, immunohistochemical, indirect immunofluorescence double staining and western blotting assays. TGF‐β1 significantly promoted the development of EndMT in a time‐dependent and dose‐dependent manner and promoted the motility and migration ability of HUVECs. The TGF‐β/Smad and Akt/mTOR/p70S6K signalling pathways were found to be associated with the pathogenesis of EndMT induced by TGF‐β1, which was also proven in vivo by the analysis of specimens from the control and CAD groups. EndMT may promote transplant kidney interstitial fibrosis by targetting the TGF‐β/Smad and Akt/mTOR/p70S6K signalling pathways, and hence, result in the development of CAD in kidney transplant recipients.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.13157</identifier><identifier>PMID: 28374926</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Adult ; AKT protein ; Akt/mTOR/p70S6K ; Assaying ; Cell Movement - drug effects ; Cells, Cultured ; chronic allograft dysfunction ; Endothelial cells ; endothelial‐to‐mesenchymal transition ; Enzyme-linked immunosorbent assay ; Epithelial-Mesenchymal Transition - drug effects ; Female ; Fibrosis ; Gene Expression - drug effects ; Human Umbilical Vein Endothelial Cells - cytology ; Human Umbilical Vein Endothelial Cells - drug effects ; Human Umbilical Vein Endothelial Cells - metabolism ; Humans ; Immunofluorescence ; Kidney - drug effects ; Kidney - metabolism ; Kidney - pathology ; kidney interstitial fibrosis ; Kidney Transplantation ; Kidney transplants ; Male ; Mesenchyme ; Motility ; Original ; Proteins ; Renal failure ; Signal transduction ; Signal Transduction - drug effects ; Smad ; Smad protein ; Tissues ; TOR protein ; Transforming Growth Factor beta1 - metabolism ; Transforming Growth Factor beta1 - pharmacology ; Transforming growth factor-b1 ; transforming growth factor‐beta1 ; Transplantation ; Transplants & implants ; Umbilical vein ; Western blotting</subject><ispartof>Journal of cellular and molecular medicine, 2017-10, Vol.21 (10), p.2359-2369</ispartof><rights>2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.</rights><rights>2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3637-cb8fe75c914128c4cdced9aae10ba7fc5faaf558429cfaf744b4b40815b49d773</citedby><cites>FETCH-LOGICAL-c3637-cb8fe75c914128c4cdced9aae10ba7fc5faaf558429cfaf744b4b40815b49d773</cites><orcidid>0000-0003-1054-9200</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1943574328/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1943574328?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,11562,25753,27924,27925,37012,37013,44590,46052,46476,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28374926$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Zijie</creatorcontrib><creatorcontrib>Han, Zhijian</creatorcontrib><creatorcontrib>Tao, Jun</creatorcontrib><creatorcontrib>Wang, Jun</creatorcontrib><creatorcontrib>Liu, Xuzhong</creatorcontrib><creatorcontrib>Zhou, Wanli</creatorcontrib><creatorcontrib>Xu, Zhen</creatorcontrib><creatorcontrib>Zhao, Chunchun</creatorcontrib><creatorcontrib>Wang, Zengjun</creatorcontrib><creatorcontrib>Tan, Ruoyun</creatorcontrib><creatorcontrib>Gu, Min</creatorcontrib><title>Role of endothelial‐to‐mesenchymal transition induced by TGF‐β1 in transplant kidney interstitial fibrosis</title><title>Journal of cellular and molecular medicine</title><addtitle>J Cell Mol Med</addtitle><description>Chronic allograft dysfunction (CAD) induced by kidney interstitial fibrosis is the main cause of allograft failure in kidney transplantation. Endothelial‐to‐mesenchymal transition (EndMT) may play an important role in kidney fibrosis. We, therefore, undertook this study to characterize the functions and potential mechanism of EndMT in transplant kidney interstitial fibrosis. Proteins and mRNAs associated with EndMT were examined in human umbilical vein endothelial cells (HUVECs) treated with transforming growth factor‐beta1 (TGF‐β1) at different doses or at different intervals with western blotting, qRT‐PCR and ELISA assays. Cell motility and migration were evaluated with motility and migration assays. The mechanism of EndMT induced by TGF‐β1 was determined by western blotting analysis of factors involved in various canonical and non‐canonical pathways. In addition, human kidney tissues from control and CAD group were also examined for these proteins by HE, Masson's trichrome, immunohistochemical, indirect immunofluorescence double staining and western blotting assays. TGF‐β1 significantly promoted the development of EndMT in a time‐dependent and dose‐dependent manner and promoted the motility and migration ability of HUVECs. The TGF‐β/Smad and Akt/mTOR/p70S6K signalling pathways were found to be associated with the pathogenesis of EndMT induced by TGF‐β1, which was also proven in vivo by the analysis of specimens from the control and CAD groups. EndMT may promote transplant kidney interstitial fibrosis by targetting the TGF‐β/Smad and Akt/mTOR/p70S6K signalling pathways, and hence, result in the development of CAD in kidney transplant recipients.</description><subject>Adult</subject><subject>AKT protein</subject><subject>Akt/mTOR/p70S6K</subject><subject>Assaying</subject><subject>Cell Movement - drug effects</subject><subject>Cells, Cultured</subject><subject>chronic allograft dysfunction</subject><subject>Endothelial cells</subject><subject>endothelial‐to‐mesenchymal transition</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Epithelial-Mesenchymal Transition - drug effects</subject><subject>Female</subject><subject>Fibrosis</subject><subject>Gene Expression - drug effects</subject><subject>Human Umbilical Vein Endothelial Cells - cytology</subject><subject>Human Umbilical Vein Endothelial Cells - drug effects</subject><subject>Human Umbilical Vein Endothelial Cells - metabolism</subject><subject>Humans</subject><subject>Immunofluorescence</subject><subject>Kidney - drug effects</subject><subject>Kidney - metabolism</subject><subject>Kidney - pathology</subject><subject>kidney interstitial fibrosis</subject><subject>Kidney Transplantation</subject><subject>Kidney transplants</subject><subject>Male</subject><subject>Mesenchyme</subject><subject>Motility</subject><subject>Original</subject><subject>Proteins</subject><subject>Renal failure</subject><subject>Signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Smad</subject><subject>Smad protein</subject><subject>Tissues</subject><subject>TOR protein</subject><subject>Transforming Growth Factor beta1 - metabolism</subject><subject>Transforming Growth Factor beta1 - pharmacology</subject><subject>Transforming growth factor-b1</subject><subject>transforming growth factor‐beta1</subject><subject>Transplantation</subject><subject>Transplants & implants</subject><subject>Umbilical vein</subject><subject>Western blotting</subject><issn>1582-1838</issn><issn>1582-4934</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>PIMPY</sourceid><recordid>eNp9kdGO1CAUhonRuOvojQ9gmnhjTGbtKVDojYmZuKtmNyZmvSaUgsNIYba0mt75CD6LD-JD-CSeteNGvRASIIfv_JzDT8hDKE8Ax7Od6fsToMDFLXIMXFZr1lB2-3AGSeURuZfzrixpDbS5S44qSQVrqvqYXL1LwRbJFTZ2adza4HX48eXrmHDpbbbRbOdeh2IcdMx-9CkWPnaTsV3RzsXl2Sly378BBhdkH3Qci4--i3bG4GiHPGIaKjjfDin7fJ_ccTpk--Cwr8j705eXm1fr87dnrzcvzteG1lSsTSudFdw0wKCShpkO32y0tlC2WjjDndaOc8mqxjjtBGMtzlICb1nTCUFX5Pmiu5_a3mJ2xAKD2g--18Oskvbq75vot-pD-qR4DbKWJQo8OQgM6WqyeVS9z8YG7NCmKSuQkkFNEUb08T_oLk1DxPYUNIxywSh--Yo8XSiDH5EH626KgVJdO6munVS_nET40Z_l36C_rUMAFuCzD3b-j5R6s7m4WER_AnRvsCM</recordid><startdate>201710</startdate><enddate>201710</enddate><creator>Wang, Zijie</creator><creator>Han, Zhijian</creator><creator>Tao, Jun</creator><creator>Wang, Jun</creator><creator>Liu, Xuzhong</creator><creator>Zhou, Wanli</creator><creator>Xu, Zhen</creator><creator>Zhao, Chunchun</creator><creator>Wang, Zengjun</creator><creator>Tan, Ruoyun</creator><creator>Gu, Min</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</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>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1054-9200</orcidid></search><sort><creationdate>201710</creationdate><title>Role of endothelial‐to‐mesenchymal transition induced by TGF‐β1 in transplant kidney interstitial fibrosis</title><author>Wang, Zijie ; Han, Zhijian ; Tao, Jun ; Wang, Jun ; Liu, Xuzhong ; Zhou, Wanli ; Xu, Zhen ; Zhao, Chunchun ; Wang, Zengjun ; Tan, Ruoyun ; Gu, Min</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3637-cb8fe75c914128c4cdced9aae10ba7fc5faaf558429cfaf744b4b40815b49d773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>AKT protein</topic><topic>Akt/mTOR/p70S6K</topic><topic>Assaying</topic><topic>Cell Movement - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cellular and molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Zijie</au><au>Han, Zhijian</au><au>Tao, Jun</au><au>Wang, Jun</au><au>Liu, Xuzhong</au><au>Zhou, Wanli</au><au>Xu, Zhen</au><au>Zhao, Chunchun</au><au>Wang, Zengjun</au><au>Tan, Ruoyun</au><au>Gu, Min</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of endothelial‐to‐mesenchymal transition induced by TGF‐β1 in transplant kidney interstitial fibrosis</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><addtitle>J Cell Mol Med</addtitle><date>2017-10</date><risdate>2017</risdate><volume>21</volume><issue>10</issue><spage>2359</spage><epage>2369</epage><pages>2359-2369</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><abstract>Chronic allograft dysfunction (CAD) induced by kidney interstitial fibrosis is the main cause of allograft failure in kidney transplantation. Endothelial‐to‐mesenchymal transition (EndMT) may play an important role in kidney fibrosis. We, therefore, undertook this study to characterize the functions and potential mechanism of EndMT in transplant kidney interstitial fibrosis. Proteins and mRNAs associated with EndMT were examined in human umbilical vein endothelial cells (HUVECs) treated with transforming growth factor‐beta1 (TGF‐β1) at different doses or at different intervals with western blotting, qRT‐PCR and ELISA assays. Cell motility and migration were evaluated with motility and migration assays. The mechanism of EndMT induced by TGF‐β1 was determined by western blotting analysis of factors involved in various canonical and non‐canonical pathways. In addition, human kidney tissues from control and CAD group were also examined for these proteins by HE, Masson's trichrome, immunohistochemical, indirect immunofluorescence double staining and western blotting assays. TGF‐β1 significantly promoted the development of EndMT in a time‐dependent and dose‐dependent manner and promoted the motility and migration ability of HUVECs. The TGF‐β/Smad and Akt/mTOR/p70S6K signalling pathways were found to be associated with the pathogenesis of EndMT induced by TGF‐β1, which was also proven in vivo by the analysis of specimens from the control and CAD groups. EndMT may promote transplant kidney interstitial fibrosis by targetting the TGF‐β/Smad and Akt/mTOR/p70S6K signalling pathways, and hence, result in the development of CAD in kidney transplant recipients.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>28374926</pmid><doi>10.1111/jcmm.13157</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-1054-9200</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of cellular and molecular medicine, 2017-10, Vol.21 (10), p.2359-2369 |
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| subjects | Adult AKT protein Akt/mTOR/p70S6K Assaying Cell Movement - drug effects Cells, Cultured chronic allograft dysfunction Endothelial cells endothelial‐to‐mesenchymal transition Enzyme-linked immunosorbent assay Epithelial-Mesenchymal Transition - drug effects Female Fibrosis Gene Expression - drug effects Human Umbilical Vein Endothelial Cells - cytology Human Umbilical Vein Endothelial Cells - drug effects Human Umbilical Vein Endothelial Cells - metabolism Humans Immunofluorescence Kidney - drug effects Kidney - metabolism Kidney - pathology kidney interstitial fibrosis Kidney Transplantation Kidney transplants Male Mesenchyme Motility Original Proteins Renal failure Signal transduction Signal Transduction - drug effects Smad Smad protein Tissues TOR protein Transforming Growth Factor beta1 - metabolism Transforming Growth Factor beta1 - pharmacology Transforming growth factor-b1 transforming growth factor‐beta1 Transplantation Transplants & implants Umbilical vein Western blotting |
| title | Role of endothelial‐to‐mesenchymal transition induced by TGF‐β1 in transplant kidney interstitial fibrosis |
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