title: Role of endothelial-to-mesenchymal transition induced by TGF-β1 in transplant kidney interstitial fibrosis.
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.
authors.affiliation: Department of Urology, the First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Zijie
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Urology, the First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Urology, the First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tao
authors.affiliation: Department of Urology, the Affiliated Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Urology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China.
authors.forename: Xuzhong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Urology, the First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Wanli
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Urology, the First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Urology, the First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Chunchun
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Urology, the First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Zengjun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Urology, the First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Ruoyun
authors.initials: R
authors.lastname: Tan
authors.affiliation: Department of Urology, the First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Min
authors.identifier: 0000-0003-1054-9200
authors.initials: M
authors.lastname: Gu
mesh_terms: D000328:Adult; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D053773:Transforming Growth Factor beta1
keywords: Akt/mTOR/p70S6K; Smad; chronic allograft dysfunction; endothelial-to-mesenchymal transition; kidney interstitial fibrosis; kidney transplantation; transforming growth factor-beta1