Antagonist targeting miR‑106b‑5p attenuates acute renal injury by regulating renal function, apoptosis and autophagy via the upregulation of TCF4

Abstract

Acute renal injury (ARI) is a life-threatening condition and a main contributor to end-stage renal disease, which is mainly caused by ischemia-reperfusion (I/R). miR-106b-5p is a kidney function-related miRNA; however, whether miR-106b-5p regulates the progression of ARI remains unclear. The present study thus aimed to examine the effects of miR-106b-5p antagonist on the regulation of ARI progression. It was found that miR-106b-5p expression was upregulated in the renal tissue of rats with I/R-induced ARI and in NRK-52E rat renal proximal tubular epithelial cells subjected to hypoxia-reoxygenation (H/R). In vitro, H/R induction suppressed the proliferation, and promoted the apoptosis and autophagy of NRK-52E cells, whereas miR-106b-5p antagonist (inhibition of miR-106b-5p) promoted the proliferation, and attenuated the apoptosis and autophagy of NRK-52E cells under the H/R condition. dual luciferase reporter gene assay validated that transcription factor 4 (TcF4) was a target of miR-106b-5p. It was further found that TcF4 overexpression promoted the proliferation, and inhibited the apoptosis and autophagy of NRK-52E cells subjected to H/R. Moreover, the effects of miR-106b-5p antagonist on NRK-52E cell proliferation, apoptosis and autophagy were mediated through the regulation of TcF4. In vivo, miR-106b-5p antagonist reduced the severity of renal injury, decreased cell proliferation in renal tissues and lowered the serum creatinine (Scr) and blood urea nitrogen (BUN) levels in the blood samples from rats with I/R-induced ARI. On the whole, the findings presented herein demonstrate that miR-106b-5p antagonist attenuates ARI by promoting the proliferation, and suppressing the apoptosis and autophagy of renal cells via upregulating TcF4.

Inhibition of MiR‐106b‐5p mediated by exosomes mitigates acute kidney injury by modulating transmissible endoplasmic reticulum stress and M1 macrophage polarization

“…27 Besides, Antagonists targeting miR-106b-5p attenuate acute kidney injury by upregulating TCF4 to modulate renal function, apoptosis, and autophagy. 28 A recent study suggested that miR-106b-5p expression levels were significantly increased in macrophages undergoing ER stress due to vitamin D deficiency, 29 which is highly in accordance with our findings. Despite a certain amount of evidence presented by these studies, it was not explored how the regulatory relationship between miR-106b-5p and ER stress was precisely controlled.…”

“…Consistent with our findings, inhibition of miR‐106b‐5p expression significantly ameliorated the progression in lipopolysaccharide (LPS)‐induced AKI 27 . Besides, Antagonists targeting miR‐106b‐5p attenuate acute kidney injury by upregulating TCF4 to modulate renal function, apoptosis, and autophagy 28 . A recent study suggested that miR‐106b‐5p expression levels were significantly increased in macrophages undergoing ER stress due to vitamin D deficiency, 29 which is highly in accordance with our findings.…”

A Systematic Review and Meta-Analysis of microRNA Profiling Studies in Chronic Kidney Diseases

“…The upregulation of miR-106b in rat kidneys subjected to ischemia/reperfusion injury reduced cell proliferation and promoted apoptosis and autophagy by targeting transcription factor 4 (TCF4) [ 100 ]. Macrophage-derived miR-106b was recently associated with inflammation-induced hypertension in mice [ 101 ].…”

Electroacupuncture-Modulated MiR-106b-5p Expression Enhances Autophagy by Targeting Beclin-1 to Promote Motor Function Recovery After Spinal Cord Injury in Rats

“…Moreover, EA treatment of SCIs in rats induces changes to miRNA expression profiles, as also demonstrated in previous studies [ 34 ]. MiR-106b-5p, a member of the 106b-25 cluster and a paralogue of the 17–92 cluster [ 35 ], has been well-studied in many diseases, including breast cance [ 35 ], and acute renal injury [ 36 ]. Recently, miR-106b-5p was found to be abnormally expressed in the spinal cords of mice models of neuropathic pain [ 4 ].…”