Renal Protection Mediated by Hypoxia Inducible Factor-1α Depends on Proangiogenesis Function of miR-21 by Targeting Thrombospondin 1

Abstract

BackgroundAngiogenesis contributes to the repair process after renal ischemia/reperfusion (I/R) injury. In the present study, we tested the role of miR-21 in the angiogenesis induced by hypoxia inducible factor (HIF)-1α through inhibiting a predicted target gene thrombospondin 1 (TSP-1).MethodsTo stabilize HIF-1α, hypoxia (1% O2 for 24 hours) was performed in human umbilical vein endothelial cells and cobalt chloride (CoCl2) was pretreated intraperitoneally 24 hours before renal I/R in mice. Locked nucleic acid modified anti-miR-21 and scrambled control was transfected with hypoxic cells or delivered into the mice via tail vein 1 hour before CoCl2 injection. The kidneys and blood were collected at 24 hours after reperfusion.ResultsHIF-1α induced by hypoxia and CoCl2 upregulated vascular endothelial growth factor and miR-21, and increased angiogenesis. It was found that expression of TSP-1 was inversely related with miR-21 in vitro and in vivo. Targeting of TSP-1 by miR-21 was further confirmed in vitro. Furthermore, HIF-1α improved renal function, accompanied with increased angiogenesis after I/R injury in mice. The protective effect of HIF-1α was attenuated by inhibition of miR-21.ConclusionsHIF-1α induced angiogenesis by upregulating not only vascular endothelial growth factor but also miR-21 via inhibiting a novel target gene TSP-1. Both of them may contribute to the protective effect of HIF-1α on renal I/R injury.

Effect of long non‐coding RNA growth arrest‐specific 5 on apoptosis in renal ischaemia/reperfusion injury

“…Induction of kidney injury by I/R in mice has been demonstrated as we performed previously . Serum creatinine level at 24 h after reperfusion significantly increased in mice from I/R group (Fig.…”

“…It plays an important role in inhibiting angiogenesis and promoting apoptosis . Our previous study has identified that up‐regulation of microRNA‐21 alleviated renal injury by promoting angiogenesis through down‐regulating expression of the novel target TSP‐1 under I/R injury condition . In addition, negative regulation between GAS5 and microRNA‐21 was discovered in Zhang's study .…”

Hypoxia alters the release and size distribution of extracellular vesicles in pancreatic cancer cells to support their adaptive survival

“…However, variability in their size exists and their true identity is only defined based on the presence of biomarkers reflecting their distinctive biogenesis. 38,39 On the other hand, the expression of Exo markers, CD9 and CD63, was detected in all (LEV, MEV and SEV) subfractions that varied between subfractions and was altered significantly under normoxia and hypoxia. 12 Exo, on the other hand, are released when multivesicular bodies exocytose.…”

Cytokine and microRNA levels during different periods of paradoxical sleep deprivation and sleep recovery in rats

“…Even when the reported recovery period was clearly not enough to a full-return to homeostasis, there are hints to suggest the presence of a repairing response. For instance, since miR-21 has been associated with the protection of various organs from suffering lesions ( Tong et al, 2015 ; Xu et al, 2017 ), the elevated levels of miR-21 seen after the 20-day recovery period posterior to 192 h of PSD may well be reflecting a mechanism aimed to restore functionality.…”