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Abstract: FR-PO924

Angiotensin II Impairs Podocyte Motility via Sirtuin-Mediated Zyxin Deacetylation and Cytoskeleton Rearrangement

Session Information

Category: Glomerular Diseases

  • 1204 Podocyte Biology

Authors

  • Bao, Dian, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HUBEI, China
  • He, Fang-Fang, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HUBEI, China
  • Zhang, Chun, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HUBEI, China
Background

Zyxin, as an adaptor protein primarily located at the adhesion plaque complex, has been implicated in the regulation of cytoskeletal dynamics and nuclear-cytoplasmic communication. However, the particular role of zyxin in regulating podocyte cytoskeleton assembly in kidney diseases remains obscure. In this study, we aimed to explore the role and mechanism of zyxin in SHR rats and AngII-treated podocytes.

Methods

The expression of zyxin and SIRT2, a mammalian homologue of NAD+-dependent deacetylase sirtuin family, were detected by western blotting, immunohistochemistry, and immunofluorescence in glomeruli of SHR rats and AngII-treated conditional immortalized human podocytes (HPCs). Co-IP was performed to assess the level of acetylated-zyxin in AngII-treated HPCs and explore the interaction between zyxin and SIRT2. AGK2, the chemical inhibitor of SIRT2, was utilized to inhibit the activity of deacetylation. Finally, the podocyte motility was assessed by migration assay.

Results

Zyxin was widely expressed in kidney tissues and HPCs. Compared with the control group, the expression of zyxin in SHR rats was unchanged, which was in line with the results in vitro. Intriguingly, podocytes exposed to AngII showed a redistribution of zyxin, which was characterized by accumulation at adhesion plaques rather than along with actins in the cytoplasm, accompanied by F-actin disarrangement. Meanwhile, we found that zyxin was deacetylated in AngII-treated podocytes. On the other hand, SIRT2 level was upregulated in glomeruli of SHR rats and dual immunofluorescence staining revealed co-localization of zyxin and SIRT2. Co-IP also suggested that SIRT2 could interact with zyxin and modulate its function through deacetylation. Finally, we found that inhibition of SIRT2 activity ameliorated podocyte motility.

Conclusion

Zyxin participated in the actin rearrangement and podocyte injury induced by AngII exposure. Our results raise the possibility that SIRT2 regulates podocyte cytoskeleton dynamics and cell motility by modulating the function of zyxin via deacetylation.

Funding

  • Government Support - Non-U.S.