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Research Paper|Volume 13, Issue 20|pp 23769—23779

Hypoxic tubular epithelial cells regulate the angiogenesis of HMEC-1 cells via mediation of Rab7/MMP-2 axis

Yiqiong Yang1, Jing Wang2, Yu Zhang1, Xiuxiu Hu1, Li Li1, Pingsheng Chen3
  • 1Department of Pathology and Pathophysiology, Medical School, Southeast University, Nanjing 210009, Jiangsu, China
  • 2Institute of Andrology, The Affiliated Drum Tower Hospital, Nanjing University, Nanjing 210008, Jiangsu, China
  • 3Institute of Nephrology, The Affiliated Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu, China
Received: July 17, 2021Accepted: October 18, 2021Published: October 25, 2021
https://doi.org/10.18632/aging.203648

Copyright: © 2021 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Renal hypoxia is associated with persisting peritubular capillary rarefaction in progression of chronic kidney disease (CKD), and this phenomenon mainly resulted from the dysregulated angiogenesis. Rab7 is known to be involved in renal hypoxia. However, the mechanism by which Rab7 regulates the renal hypoxia remains unclear. Protein expression was detected by western blot. Cell proliferation was detected by EdU staining. Cell migration was tested by transwell assay. Rab7 was upregulated in HK-2 cells under hypoxia conditions. Hypoxia significantly inhibited the viability and proliferation of human microvascular endothelial cells (HMEC-1 cells), while this phenomenon was obviously reversed by Rab7 silencing. Consistently, Hypoxia significantly decreased the migration and tube length of HMECs, which was partially reversed by knockdown of Rab7. Moreover, hypoxia-induced inhibition of MMP2 activity was significantly rescued by knockdown of Rab7. Moreover, ARP100 (MMP-2 inhibitor) significantly reversed the effect of Rab7 shRNA on cell viability, migration and angiogenesis. Furthermore, knockdown of Rab7 significantly alleviated the fibrosis in tissues of mice. Knockdown of Rab7 significantly alleviated the renal hypoxia in chronic kidney disease through regulation of MMP-2. Thus, our study might shed new light on exploring the new strategies against CKD.