Hedgehog pathway plays a vital role in HIV-induced epithelial-mesenchymal transition of podocyte.

Abstract:

:HIV-associated nephropathy (HIVAN) is characterized by heavy proteinuria, rapidly progressive renal failure, and distinct morphological features in the kidney. HIV-induced epithelial-mesenchymal transition (EMT) is critically important for the progression of kidney injury. In this study, we tested the role of hedgehog pathway in the HIV-induced EMT and fibrosis of kidney. We used the Tg26 mice, the abundantly used HIVAN mouse model, to investigate the activation of hedgehog pathway by HIV. Western blotting and real time PCR results showed that renal tissue expression of hedgehog pathway related molecules, including hedgehog homologous (Shh, Ihh, Dhh), PTCH, and Gli1, were increased in HIVAN (Tg26) mice; while immunofluorescent staining displayed localization PTCH expression in podocytes. For in vitro studies, we used recombinant sonic hedgehog (Shh) and HIV for their expression by podocytes. Both the methods activated the hedgehog pathway, enhanced the expression of EMT markers, and decreased impermeability. Overexpression of Gli1 by human podocytes also augmented their expression of EMT markers. On the other hand, the blockade of hedgehog pathway with Gant 58, a specific blocker for Gli1-induced transcription, dramatically decreased HIV-induced podocyte EMT and permeability. These results indicate that hedgehog pathway plays an important role in HIV-induced podocyte injury. The present study provides mechanistical insight into a new target for therapeutic strategy.

journal_name

Exp Cell Res

authors

Lan X,Wen H,Cheng K,Plagov A,Marashi Shoshtari SS,Malhotra A,Singhal PC

doi

10.1016/j.yexcr.2017.01.019

subject

Has Abstract

pub_date

2017-03-15 00:00:00

pages

193-201

issue

2

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(17)30030-7

journal_volume

352

pub_type

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