BMP-7 Blocks the Cyclosporine-A-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells. Export

@article{citeulike:6031332, abstract = {Aims: The nephrotoxic side effects of cyclosporine A (CsA) are partly due to induction of the epithelial-to-mesenchymal transition (EMT), possibly through upregulation of connective tissue growth factor (CTGF). Bone morphogenetic protein (BMP-7) has been reported to protect against and reverse renal injury via its renotropic and antifibrotic effects. We therefore designed a method to investigate the mechanism by which BMP-7 inhibits CSA-induced EMT in cultured human renal proximal tubular epithelial (HK-2) cells and whether BMP-7 can antagonize CsA-induced profibrogenic effects. Methods: Cultured HK-2 cells were treated with CsA or a combination of CsA and BMP-7 for 72 h. Morphological changes were assessed by phase-contrast microscopy. The expression of alpha-smooth muscle actin (alpha-SMA), E-cadherin, collagen type I and CTGF was analyzed by immunofluorescence, RT-PCR, and Western blot. Additionally, the effect of CTGF silencing on CsA-mediated gene expression was assessed. Results: CsA-induced EMT was associated with decreased expression of E-cadherin, increased expression of alpha-SMA, collagen type I and CTGF, and loss of epithelial morphology. BMP-7 inhibited these effects in a dose-dependent manner. Using siRNA, CTGF knock-down also attenuated EMT-associated phenotypic changes induced by CsA. Conclusion: These data suggest that BMP-7 can block CsA-induced EMT by downregulating the expression of CTGF, a downstream mediator of EMT.}, author = {Xu, Yanfang and Wan, Jianxin and Jiang, Dewen and Wu, Xiaonan}, citeulike-article-id = {6031332}, citeulike-linkout-0 = {http://dx.doi.org/10.1159/000245063}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19816049}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19816049}, day = {9}, doi = {10.1159/000245063}, issn = {1660-2129}, journal = {Nephron. Experimental nephrology}, keywords = {bmp, csa, emt, pt}, month = {October}, number = {1}, posted-at = {2009-10-29 06:08:04}, priority = {2}, title = {BMP-7 Blocks the Cyclosporine-A-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells.}, url = {http://dx.doi.org/10.1159/000245063}, volume = {114}, year = {2009} }

TY - JOUR ID - citeulike:6031332 L3 - citeulike-article-id:6031332 N2 - Aims: The nephrotoxic side effects of cyclosporine A (CsA) are partly due to induction of the epithelial-to-mesenchymal transition (EMT), possibly through upregulation of connective tissue growth factor (CTGF). Bone morphogenetic protein (BMP-7) has been reported to protect against and reverse renal injury via its renotropic and antifibrotic effects. We therefore designed a method to investigate the mechanism by which BMP-7 inhibits CSA-induced EMT in cultured human renal proximal tubular epithelial (HK-2) cells and whether BMP-7 can antagonize CsA-induced profibrogenic effects. Methods: Cultured HK-2 cells were treated with CsA or a combination of CsA and BMP-7 for 72 h. Morphological changes were assessed by phase-contrast microscopy. The expression of alpha-smooth muscle actin (alpha-SMA), E-cadherin, collagen type I and CTGF was analyzed by immunofluorescence, RT-PCR, and Western blot. Additionally, the effect of CTGF silencing on CsA-mediated gene expression was assessed. Results: CsA-induced EMT was associated with decreased expression of E-cadherin, increased expression of alpha-SMA, collagen type I and CTGF, and loss of epithelial morphology. BMP-7 inhibited these effects in a dose-dependent manner. Using siRNA, CTGF knock-down also attenuated EMT-associated phenotypic changes induced by CsA. Conclusion: These data suggest that BMP-7 can block CsA-induced EMT by downregulating the expression of CTGF, a downstream mediator of EMT. IS - 1 JF - Nephron. Experimental nephrology SN - 1660-2129 TI - BMP-7 Blocks the Cyclosporine-A-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells. VL - 114 KW - bmp KW - csa KW - emt KW - pt AU - Xu, Yanfang AU - Wan, Jianxin AU - Jiang, Dewen AU - Wu, Xiaonan PY - 2009/10/09/ UR - http://dx.doi.org/10.1159/000245063 ER -