Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Hypoxic Tubular Epithelial Cells Regulating Angiogenesis by Rab 7

Version 1 : Received: 12 March 2021 / Approved: 15 March 2021 / Online: 15 March 2021 (10:33:05 CET)

How to cite: Yang, Y.; Wang, J.; Zhang, Y.; Hu, X.; Li, L.; Chen, P. Hypoxic Tubular Epithelial Cells Regulating Angiogenesis by Rab 7. Preprints 2021, 2021030364 (doi: 10.20944/preprints202103.0364.v1). Yang, Y.; Wang, J.; Zhang, Y.; Hu, X.; Li, L.; Chen, P. Hypoxic Tubular Epithelial Cells Regulating Angiogenesis by Rab 7. Preprints 2021, 2021030364 (doi: 10.20944/preprints202103.0364.v1).

Abstract

The purpose of our study was to discuss Rab 7 effects in chronic kidney disease (CKD). Methods: Using WT and Rab 7-/- mice as target animal, and HK-2 and HMEC-1 cell co-cultured to make cell model. Measuring kidney tissues were evaluated by Sirius red staining, immunohistochemistry staining to CD 34 protein, Transmission electron microscope (TEM) and gelatin zymography to MMP-2 activities. The cell proliferation were measured by CCK-8 and Ki67 protein expression. Measuring cell invasion and total length were evaluated by transwell and in vitro angiogenesis assay. MMP-2 activities were evaluated by gelatin zymography in cell groups. The relative proteins expression were evaluated by Western blot in kidney tissues and cell groups. Results: Hypoxia promoted the expression of Rab7 in HMEC-1, and the activity of MMP-2 related with regulatory molecules such as reversion-inducing-cysteine-rich protein with kazal motifs (RECK), negative correlation with membrane-type 1 MMP (MT1-MMP or MMP-14) on the membrane of TECs. In addition, the up-regulation of the expression of Rab7 inhibited the activity of MMP-2 and proliferation and cyclization of endothelial cells, and the inhibitor of MMP-2 partially blocked the effects of Rab7 on angiogenesis. Furthermore, the similar data were also obtained in the fibrosis kidney tissues of mice. Conclusion: Rab 7 might be an important role in hypoxic TECs regulated angiogenesis, Rab 7 knockdown could improve hypoxic TECs regulated angiogenesis, the relative mechanisms might be correlation with RECK pathway and MMP-2 activities in vivo and vitro study.

Subject Areas

Rab 7; hypoxic; HMEC-1; MMP-2 activity; RECK

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