miR-210 Protects Renal Cell Against Hypoxia-induced Apoptosis by Targeting HIF-1 Alpha

Abstract

The kidney is vulnerable to hypoxia-induced injury. One of the mechanisms underlying this phenomenon is cell apoptosis triggered by hypoxia-inducible factor-1-α (HIF-1α) activation. ) is known to be induced by HIF-1α and can regulate various pathological processes, but its role in hypoxic kidney injury remains unclear. Here, in both rat systemic hypoxia and local kidney hypoxia models, we found miR-210 levels were upregulated significantly in injured kidney, especially in renal tubular cells. A similar increase was observed in hypoxia-treated human renal tubular HK-2 cells. We also verified that miR-210 can directly suppress HIF-1α expression by targeting the 3′ untranslated region of HIF-1α mRNA in HK-2 cells in severe hypoxia. Accordingly, miR-210 overexpression caused significant inhibition of the HIF-1α pathway and attenuated apoptosis caused by hypoxia, while miR-210 knockdown exerted the opposite effect. Taken together, our findings verify that miR-210 is involved in the molecular response in hypoxic kidney lesions in vivo and attenuates hypoxia-induced renal tubular cell apoptosis by targeting HIF-1α directly and suppressing HIF-1α pathway activation in vitro.

Immunomodulatory and Regenerative Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Renal Diseases

“…In addition, Liu et al reported that miR-145 ameliorated TGF-β1-induced EMT in renal proximal tubular cells possibly by inhibiting TGF-β-smad signaling pathway [58]. In the same line, Liu et al, reported that miR-145 overexpression inhibited high-glucose-induced EMT and fibrosis via downregulating ZEB2 [59]. Therefore, miR-145 might be the promising target to protect from kidney injury through the regulation of autophagy and EMT.…”

Effects of hypoxic‑ischemic pre‑treatment on microvesicles derived from endothelial progenitor cells

“…In specific cell types, including primary vascular ECs, hypoxia induces an augmented expression of miR-210 (38,41). Data on the genetic structure indicate that the promoter region of miR-210 carries a functioning hypoxia response element (HRE), which may be recognized by hypoxia-inducible factor-1α for the induction of miRNA transcription upon exposure to hypoxia (42,43). Thus, miR-210 is sensitive to hypoxic stimuli and has an important role in modulating hypoxia-induced pathogeneses.…”

Dexmedetomidine post‐treatment attenuates cardiac ischaemia/reperfusion injury by inhibiting apoptosis through HIF‐1α signalling

“…Under this condition, treatments that inhibited the HIF‐1α activity reduced I/R and H/R injuries in rat hearts and cardiomyocytes, respectively, which is in line with our results. A recent study also revealed that miR‐210 reduces the renal tubular cell apoptosis that occurs in response to hypoxia by suppressing HIF‐1α pathway activation . The inconsistency between the pro‐survival and the pro‐apoptotic effects of HIF‐1α may be attributable to differences in cell environments and the severity of hypoxia.…”