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

Abstract

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.

MicroRNAs in Transforming Growth Factor-Beta Signaling Pathway Associated With Fibrosis Involving Different Systems of the Human Body

“…JAK, which is a receptor-associated tyrosine kinase, acts as regulators of cytokine and growth factor signaling. JAK2 is a regulator of the profibrotic results of TGF-β in many fibrotic diseases ( O'Shea et al, 2015 ; Cao et al, 2019 ; Zhao et al, 2019 ; Qin et al, 2020 ). STAT3, a STAT protein and a downstream regulator of JAK2 signaling, is crucial to many fibrotic diseases in a TGF-β-dependent manner ( O'Shea et al, 2015 ; Chakraborty et al, 2017 ; Oh et al, 2018 ).…”

Periodontitis aggravates kidney injury by upregulating STAT1 expression in a mouse model of hypertension

“…STAT is widely involved in cell proliferation, apoptosis, and tumorigenesis, and is also related to the occurrence and development of a variety of diseases [13]. Activation of the JAK/STAT1 pathway can upregulate the expression of pro‐inflammatory factor interleukin (IL)‐1 and pro‐fibrotic factor tumor growth factor (TGF)‐β in the kidney; thus, STAT1 may be a potential therapeutic target for CKD [14]. Saraiva et al .…”

“…STAT is widely involved in cell proliferation, apoptosis, and tumorigenesis, and is also related to the occurrence and development of a variety of diseases [13]. Activation of the JAK/STAT1 pathway can upregulate the expression of pro-inflammatory factor interleukin (IL)-1 and pro-fibrotic factor tumor growth factor (TGF)-b in the kidney; thus, STAT1 may be a potential therapeutic target for CKD [14]. Saraiva et al revealed the association between a STAT1 gene polymorphism and the development of severe periodontitis, while Haftcheshmeh et al showed that STAT1 is upregulated in the periodontal tissue of patients with periodontitis [15,16].…”

PERK-Dependent Activation of the JAK2/STAT3 Pathway Contributes to High Glucose-Induced Extracellular Matrix Deposition in Renal Tubular Epithelial Cells

“…It is, however, unclear that how high glucose induces the expression of TGF-β1 and ECM accumulation. e JAK/ STAT pathway is a crucial signal transduction cascade that regulates cellular activation, proliferation, and inflammation, and the activation of the JAK/STAT-signaling pathway leads to the development of fibrosis in the lung and kidney via the induction of TGF-β1 and collagens [17,18]. A STAT3 inhibitor suppressed TGF-β1 so as to prevent the occurrence of DKD in STZ-induced rats [19], while it was also reported that JAK2/STAT3 signaling may play a role in the renal fibrosis repair process in mice with UUO (unilateral ureteral obstruction) and that this effect was partially mediated by MMP-2 activation.…”