Dab1 Contributes to Angiotensin II-Induced Apoptosis via p38 Signaling Pathway in Podocytes.

Zhao Gao,Ping Zeng,Guohua Ding,Xinghua Chen,Kai Zhu

doi:10.1155/2017/2484303

Zhao Gao, Ping Zeng + Show 3 more

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https://doi.org/10.1155/2017/2484303

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Abstract

Numerous studies have found that angiotensin II (Ang II) participates in podocyte apoptosis and exacerbates progression of end-stage kidney disease (ESKD). However, its underlying mechanism remains largely unexplored. As a homolog of Drosophila disabled (Dab) protein, Dab1 plays a vital role in cytoskeleton, neuronal migration, and proliferation. In the present study, our data revealed that Ang II-infused rats developed hypertension, proteinuria, and podocyte injury accompanied by Dab1 phosphorylation and increased reelin expression in kidney. Moreover, Ang II induced podocyte apoptosis in vitro. Dab1 phosphorylation and reelin expression in podocytes were increased after exposure to Ang II. Conversely, Dab1 small interfering RNA (siRNA) exerted protective effects on Ang II-induced podocyte apoptosis, resulting in decreased p38 phosphorylation and reelin expression. These results indicated that Dab1 mediated Ang II-induced podocyte apoptosis via p38 signaling pathway.

Highlights

As terminally differentiated cells, podocytes play a crucial role in establishing the integrity and selective permeability of the glomerular filtration barrier [1,2,3]
Our data revealed that angiotensin II (Ang II) exposure significantly increased podocyte apoptosis (Figure 3(e))
We reported that Dab1 contributed to Ang II-induced podocyte apoptosis via p38 signaling pathway

Summary

Introduction

Podocytes play a crucial role in establishing the integrity and selective permeability of the glomerular filtration barrier [1,2,3]. Accumulating evidence has shown that podocyte injury is associated with proteinuria and several glomerular diseases [4,5,6,7]. Recent studies have shown that Ang II can induce podocyte apoptosis both in vivo and in vitro [10,11,12]. A secreted extracellular matrix glycoprotein, or apoE binds to very low-density lipoprotein receptor (VLDLR) and/or apolipoprotein receptor 2 (ApoER2), Dab interacts with the SH2 domains of Src, Fyn, and Abl, leading to Dab tyrosine phosphorylation and activation of downstream signaling pathways, such as Crk-C3G-Rap1-cadherin pathway and PI3K-Akt pathway [14]. Our previous study has indicated that c-Abl upregulation promotes podocyte apoptosis upon exposure to Ang II via Akt signaling [12]. We hypothesized that Dab participated in podocyte apoptosis and aimed to examine the role of Dab in Ang II-induced podocyte apoptosis and signal transduction

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