microRNA‐206 overexpression inhibits epithelial‐mesenchymal transition and glomerulosclerosis in rats with chronic kidney disease by inhibiting JAK/STAT signaling pathway

• Published in: Journal of cellular biochemistry 2019-09, Vol.120 (9), p.14604-14617
• Main Authors: Zhao, Shi‐Qi, Shen, Zhao‐Chun, Gao, Bing‐Feng, Han, Ping
• Format: Article
• Language: English
• Subjects: chronic kidney disease; Clear cell-type renal cell carcinoma; Collagen; Collagen (type IV); Degeneration; Epithelial cells; epithelial‐mesenchymal transition; Fibrosis; glomerulosclerosis; Growth factors; Interleukins; JAK/STAT signaling pathway; Janus kinase 2; Kidney diseases; Kidneys; Mesenchyme; MicroRNAs; microRNA‐206; miRNA; Ribonucleic acid; RNA; Sclerosis; Signal transduction; Signaling; Stat1 protein; Stat3 protein; Transforming growth factor-b1; Vimentin
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.28722

Chronic kidney disease (CKD) is a traumatic disease with significant psychic consequences to the patient's overall physical condition. microRNA‐206 (miR‐206) has been reported to play an essential role in the development of various diseases. The purpose of the present study is to investigate the effect of miR‐206 through the JAK/STAT signaling pathway on epithelial‐mesenchymal transition (EMT) of renal tubular epithelial cells and glomerulosclerosis in rats with CKD. The targeting relationship between miR‐206 and ANXA1 was verified. To explore the role of miR‐206 in CKD, the model of CKD rats was established to detect glomerular sclerosis index (GSI), contents of interleukin‐6 (IL‐6) and transforming growth factor‐beta1 (TGF‐β1), and expression of type IV collagen. Moreover, to further determine the roles of both miR‐206 and the JAK/STAT signaling pathway in CKD, the gain‐ and loss‐of function approaches were performed with the expression of ANXA1, α‐SMA, E‐cadherin, vimentin, N‐cadherin, and the JAK/STAT signaling pathway‐related genes detected. miR‐206 negatively targeted ANXA1. Overexpressed miR‐206 inhibited the degeneration and interstitial fibrosis of renal tubular epithelial cells, decreased GSI of rats, and the expression of type IV collagen, TGF‐β1 and IL‐6. Overexpressed miR‐206 inhibited the degeneration of renal tubular epithelial cells, the expression of ANXA1, α‐SMA, TGF‐β1, p‐STAT3, STAT3, p‐STAT1, STAT1, p‐JAK2, and JAK2, while promoted the expression of E‐cadherin. Taken together the results, miR‐206 inhibits EMT of renal tubular epithelial cells and glomerulosclerosis by inactivating the JAK/STAT signaling pathway via ANXA1 in CKD.