Transplantation of endothelial progenitor cells alleviates renal interstitial fibrosis in a mouse model of unilateral ureteral obstruction.

摘要

AIMS: The present study investigated whether transplantation of bone marrow-derived endothelial progenitor cells (BM-EPCs) in renal capillary network improves renal interstitial fibrosis in unilateral ureteral obstruction (UUO) model in mice. MAIN METHODS: Ex vivo generated, characterized, and cultivated mice BM-EPCs were identified by their vasculogenic properties in vitro. BM-EPCs were labelled with carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) before transplantation. The animal models of UUO were used. Histological changes in renal tubular interstitium were observed with HE and Masson staining. The protein levels of vascular endothelial growth factor(VEGF), hypoxia inducible factor-1alpha (HIF-1alpha) and connective tissue growth factor (CTGF) were analyzed by western blotting and immunohistochemistry. Transforming growth factor-beta1 (TGF-beta1) was detected by immunohistochemistry. Peritubular capillary (PTC) density was determined by CD31 immunostaining. KEY FINDINGS: Transplanted BM-EPCs were successfully incorporated into the capillary network in the obstructed kidney in vivo. UUO induced a significant decrease in VEGF levels and PTC density in the kidney tissue, which was accompanied by a significant increase in HIF-1alpha, CTGF and TGF-beta1. Transplantation of BM-EPCs increased PTC density, VEGF expression and alleviated the development of renal interstitial fibrosis in UUO mice. No significant pathological changes were found in control mice. SIGNIFICANCE: The reduction of PTC density and up-regulation of HIF-1alpha are the important mechanisms of interstitial fibrosis in UUO mice. BM-EPCs transplantation may increase the number of capillary density and alleviate the development of renal fibrosis in obstructive nephropathy in mice.