P53 induces miR199a-3p to suppress SOCS7 for STAT3 activation and renal fibrosis in UUO

Ruhao Yang, Xuan Xu, Huiling Li, Jinwen Chen, Xudong Xiang, Zheng Dong, Dongshan Zhang

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The role of p53 in renal fibrosis has recently been suggested, however, its function remains controversial and the underlying mechanism is unclear. Here, we show that pharmacological and genetic blockade of p53 attenuated renal interstitial fibrosis, apoptosis, and inflammation in mice with unilateral urethral obstruction (UUO). Interestingly, p53 blockade was associated with the suppression of miR-215-5p, miR-199a-5p&3p, and STAT3. In cultured human kidney tubular epithelial cells (HK-2), TGF-β1 treatment induced fibrotic changes, including collagen I and vimentin expression, being associated with p53 accumulation, p53 Ser15 phosphorylation, and miR-199a-3p expression. Inhibition of p53 by pifithrin-α blocked STAT3 activation and the expression of miR-199a-3p, collagen I, and vimentin during TGF-β1 treatment. Over-expression of miR-199a-3p increased TGFβ1-induced collagen I and vimentin expression and restored SOCS7 expression. Furthermore, SOCS7 was identified as a target gene of miR-199a-3p, and silencing of SOCS7 promoted STAT3 activation. ChIp analyses indicated the binding of p53 to the promoter region of miR-199a-3p. Consistently, kidney biopsies from patients with IgA nephropathy and diabetic nephropathy exhibited substantial activation of p53 and STAT3, decreased expression of SOCS7, and increase in profibrotic proteins and miR-199a-3p. Together, these results demonstrate the novel p53/miR-199a-3p/SOCS7/STAT3 pathway in renal interstitial fibrosis.

Original languageEnglish (US)
Article number43409
JournalScientific Reports
Volume7
DOIs
StatePublished - Feb 27 2017

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Urethral Obstruction
Fibrosis
Kidney
Vimentin
Collagen
Diabetic Nephropathies
Genetic Promoter Regions
Immunoglobulin A
Epithelial Cells
Phosphorylation
Pharmacology
Apoptosis
Inflammation
Biopsy
Therapeutics
Genes
Proteins

ASJC Scopus subject areas

  • General

Cite this

P53 induces miR199a-3p to suppress SOCS7 for STAT3 activation and renal fibrosis in UUO. / Yang, Ruhao; Xu, Xuan; Li, Huiling; Chen, Jinwen; Xiang, Xudong; Dong, Zheng; Zhang, Dongshan.

In: Scientific Reports, Vol. 7, 43409, 27.02.2017.

Research output: Contribution to journalArticle

Yang, Ruhao ; Xu, Xuan ; Li, Huiling ; Chen, Jinwen ; Xiang, Xudong ; Dong, Zheng ; Zhang, Dongshan. / P53 induces miR199a-3p to suppress SOCS7 for STAT3 activation and renal fibrosis in UUO. In: Scientific Reports. 2017 ; Vol. 7.
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