[Role of TGF-?1/ILK/FSP1 signaling pathway in cyclosporin A-induced epithelialmesenchymal transition in cultured renal tubular epithelial cells].
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ABSTRACT: OBJECTIVE:To explore the role of transforming growth factor-?1/integrin-linked kinase/fibroblast-specific protein 1 (TGF- ?1/ILK/FSP1) signaling pathway in cyclosporine A (CsA)-induced renal tubular epithelial cell transdifferentiation. METHODS:Rat renal tubular epithelial NRK-52E cells were induced with 1 mg/L CsA, treated with TGF-?1 inhibitor (SB431542, 10 ?mol/L), or transfected with the ILK-RNAi lentiviral expression vector (ILKshRNA) or a negative control vector before CsA induction. The expressions of TGF-?1, ILK and FSP-1 mRNAs and proteins in the cells were detected using real-time PCR and Western blotting. The positive cells for ?-SMA expression were detected by immunohistochemistry. RESULTS:Compared with the blank control cells, the cells treated with CsA showed significantly increased levels of TGF-?1, ILK and FSP-1 mRNAs and proteins (P < 0.05). The expressions of TGF-?1, ILK and FSP-1 were significantly lower in TGF-?1 inhibitor group than in CsA group (P < 0.05). The levels of ILK and FSP-1 were significantly decreased after shRNA-mediated ILK silencing (P < 0.05). The number of positive cells for ?-SMA was significantly lower in cells treated with SB431542 and in cells with ILK silencing than in the cells treated with CsA alone (P < 0.05). CONCLUSIONS:The activation of TGF-?1/ILK/FSP-1 signaling pathway is an important mechanism for CsA-induced transdifferentiation in rat renal tubular epithelial cells. ILK participates in CsA-induced epithelialmesenchymal transition of renal tubular epithelial cells.
SUBMITTER: Bai Z
PROVIDER: S-EPMC6765554 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
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