Role of TGF-β1/ILK/FSP1 signaling pathway in cyclosporin A-induced epithelialmesenchymal transition in cultured renal tubular epithelial cells.
10.12122/j.issn.1673-4254.2019.07.09
- Author:
Zhixun BAI
1
;
Jing LU
2
;
Yibin YANG
3
Author Information
1. Department of Nephrology and Rheumatology, Second Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China.
2. Zunyi Medical and Pharmaceutical College, Zunyi 563006, China.
3. Department of Nephrology, Affiliated Hospital of Zunyi Medical University, Zunyi 563006, China.
- Publication Type:Journal Article
- Keywords:
chronic cyclosporine nephropathy;
epithelial-mesenchymal transition;
fibroblast-specific protein 1;
integrinlinked kinase;
transforming growth factor-β1
- MeSH:
Animals;
Calcium-Binding Proteins;
Cells, Cultured;
Cyclosporine;
Epithelial Cells;
Epithelial-Mesenchymal Transition;
Protein-Serine-Threonine Kinases;
Rats;
Signal Transduction;
Transforming Growth Factor beta1
- From:
Journal of Southern Medical University
2019;39(7):804-809
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the role of transforming growth factor-β1/integrin-linked kinase/fibroblast-specific protein 1 (TGF- β1/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-β1 inhibitor (SB431542, 10 μmol/L), or transfected with the ILK-RNAi lentiviral expression vector (ILKshRNA) or a negative control vector before CsA induction. The expressions of TGF-β1, ILK and FSP-1 mRNAs and proteins in the cells were detected using real-time PCR and Western blotting. The positive cells for α-SMA expression were detected by immunohistochemistry.
RESULTS:Compared with the blank control cells, the cells treated with CsA showed significantly increased levels of TGF-β1, ILK and FSP-1 mRNAs and proteins ( < 0.05). The expressions of TGF-β1, ILK and FSP-1 were significantly lower in TGF-β1 inhibitor group than in CsA group ( < 0.05). The levels of ILK and FSP-1 were significantly decreased after shRNA-mediated ILK silencing ( < 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 ( < 0.05).
CONCLUSIONS:The activation of TGF-β1/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.
