Faculty Collaboration Database

Renal Protection Mediated by Hypoxia Inducible Factor-1α Depends on Proangiogenesis Function of miR-21 by Targeting Thrombospondin 1. Transplantation 2017 Aug;101(8):1811-1819

Date

07/25/2017

Pubmed ID

28737660

Pubmed Central ID

PMC5542793

DOI

10.1097/TP.0000000000001501

Scopus ID

2-s2.0-84988948408 (requires institutional sign-in at Scopus site)   45 Citations

Abstract

BACKGROUND: Angiogenesis 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).

METHODS: To 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.

RESULTS: HIF-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.

CONCLUSIONS: HIF-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.

Author List

Xu X, Song N, Zhang X, Jiao X, Hu J, Liang M, Teng J, Ding X

MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis
Blotting, Western
Cells, Cultured
Disease Models, Animal
Follow-Up Studies
Gene Expression Regulation
Human Umbilical Vein Endothelial Cells
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
Immunohistochemistry
In Situ Hybridization
Kidney
Male
Mice
Mice, Inbred C57BL
MicroRNAs
Neovascularization, Pathologic
RNA
Real-Time Polymerase Chain Reaction
Reperfusion Injury
Signal Transduction
Thrombospondin 1
Time Factors