Integrin α 5 Is Regulated by miR-218-5p in Endothelial Progenitor Cells.

Autor:	Liu J; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Nephrology, Department of Medicine, Guangzhou University of Chinese Medicine, The Second Affiliated Hospital of Chinese Medicine, Guangzhou, China., Li Y; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Lyu L; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Department of Molecular Biology, Beijing Chest Hospital, Capital Medical University, Beijing, China., Xiao L; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Department of Surgery and Oncology, Shenzhen Second People's Hospital/the First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China., Memon AA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Yu X; Blood Transfusion Research Institute, Wuxi Red Cross Blood Center, Wuxi, Jiangsu, China., Halim A; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Patel S; Division of Nephrology, Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts., Osman A; Harvard College, Cambridge, Massachusetts., Yin W; Division of Nephrology, Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts., Jiang J; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts., Naini S; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Lim K; Division of Nephrology, Indiana University School of Medicine, Indianapolis, Indiana., Zhang A; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Williams JD; DNA Identification Testing Division, Laboratory Corporation of America Holdings, Burlington, North Carolina., Koester R; DNA Identification Testing Division, Laboratory Corporation of America Holdings, Burlington, North Carolina., Qi KZ; Boston College, Boston, Massachusetts., Fucci QA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Ding L; Program for Interdisciplinary Neuroscience, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Chang S; Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Patel A; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Mori Y; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Chaudhari A; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Bao A; Washington University in St. Louis, St. Louis, Missouri., Liu J; Shenzhen Jiake Biotechnology, Shenzhen, China., Lu TS; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Siedlecki A; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Jazyk:	angličtina
Zdroj:	Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2022 Mar; Vol. 33 (3), pp. 565-582. Date of Electronic Publication: 2022 Jan 28.
DOI:	10.1681/ASN.2021020140
Abstrakt:	Background: Endothelial cell injury is a common nidus of renal injury in patients and consistent with the high prevalence of AKI reported during the coronavirus disease 2019 pandemic. This cell type expresses integrin α 5 (ITGA5), which is essential to the Tie2 signaling pathway. The microRNA miR-218-5p is upregulated in endothelial progenitor cells (EPCs) after hypoxia, but microRNA regulation of Tie2 in the EPC lineage is unclear. Methods: We isolated human kidney-derived EPCs (hkEPCs) and surveyed microRNA target transcripts. A preclinical model of ischemic kidney injury was used to evaluate the effect of hkEPCs on capillary repair. We used a genetic knockout model to evaluate the effect of deleting endogenous expression of miR-218 specifically in angioblasts. Results: After ischemic in vitro preconditioning, miR-218-5p was elevated in hkEPCs. We found miR-218-5p bound to ITGA5 mRNA transcript and decreased ITGA5 protein expression. Phosphorylation of 42/44 MAPK decreased by 73.6% in hkEPCs treated with miR-218-5p. Cells supplemented with miR-218-5p downregulated ITGA5 synthesis and decreased 42/44 MAPK phosphorylation. In a CD309-Cre/miR-218-2-LoxP mammalian model (a conditional knockout mouse model designed to delete pre-miR-218-2 exclusively in CD309 + cells), homozygotes at e18.5 contained avascular glomeruli, whereas heterozygote adults showed susceptibility to kidney injury. Isolated EPCs from the mouse kidney contained high amounts of ITGA5 and showed decreased migratory capacity in three-dimensional cell culture. Conclusions: These results demonstrate the critical regulatory role of miR-218-5p in kidney EPC migration, a finding that may inform efforts to treat microvascular kidney injury via therapeutic cell delivery. (Copyright © 2022 by the American Society of Nephrology.)
Databáze:	MEDLINE
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