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Cellular senescence as a target to inhibit epithelial‐mesenchymal transition in HK‐2 cells
Author(s) -
Xie Dengpiao,
Hu Gaizun,
Chen Chaoling,
Wang Weili,
Gewirtz David,
Li Ningjun
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.04373
Subject(s) - senescence , epithelial–mesenchymal transition , western blot , transforming growth factor , biology , endocrinology , secretion , medicine , blot , cancer research , mesenchymal stem cell , chemistry , microbiology and biotechnology , transition (genetics) , biochemistry , gene
Cellular senescence is a program that induces a stable growth arrest accompanied by metabolic reprogramming, phenotypic changes, increased senescence‐associated β‐galactosidase (SA‐β‐gal) activity, and secretion of senescence‐associated secretory phenotype. It has been demonstrated that cellular senescence is associated with epithelial‐mesenchymal transition (EMT) and chronic kidney disease, and higher SA‐β‐gal activity were found in proximal and distal tubules of feline chronic kidney disease (CKD). Studies showed that elimination of senescent cells by FOXO4 DRI, a peptide antagonist to block the interaction of forkhead box O 4 (FOXO4) and p53, improved kidney function in aging mice. The represent study tested the hypothesis that inhibition of cellular senescence alleviates TGF‐β1‐induced EMT in human renal epithelial (HK‐2) cells. Cultured HK‐2 cells were divided into 3 groups: Ctrl, TGF‐β1 and FOXO4 DRI+TGF‐β1. Western blot analysis showed that a senescent biomarker, p16, was significantly higher in TGF‐β1 group than that in Ctrl and F+ TGF‐β1 groups (1±0.15, 2±0.1, 0.96±0.15 in Ctrl, TGF‐β1, F+ TGF‐β1 group, respectively, p<0.05). Another important senescent indicator, SA‐β‐gal staining, was also significantly increased in TGF‐β1 group than that in Ctrl and F+ TGF‐β1 groups(1±0.27, 7.2±0.39, 4.6±0.38 in Ctrl, TGF‐β1, F+ TGF‐β1 group, respectively, p<0.05). Meanwhile, Western blot analysis showed that the EMT markers, α‐SMA and collagen I/III, were significantly higher in TGF‐β1 group than that in Ctrl and F+ TGF‐β1 groups (α‐SMA1±0.05, 1.4±0.05, 0.96±0.1 in Ctrl, TGF‐β1, F+ TGF‐β1 group, respectively, p<0.05; and collagen I/III: 1±0.03, 1.49±0.06, 0.91±0.1 in Ctrl, TGF‐β1, F+ TGF‐β1 group, respectively, p<0.05). These results suggest that targeting cellular senescence might be a potential therapeutic strategy for CKD.