The Pathophysiologic Role of Gelsolin in Chronic Kidney Disease: Focus on Podocytes

Yu, Chia-Jung; Damaiyanti, Dian W.; Yan, Shian-Jang; Wu, Chih-Hsing; Tang, Ming-Jer; Shieh, Dar-Bin; Liu, Peter P.; Liu, Ping-Yen

doi:10.3390/ijms222413281

Open AccessArticle

The Pathophysiologic Role of Gelsolin in Chronic Kidney Disease: Focus on Podocytes

by

Chia-Jung Yu

^1,†,

Dian W. Damaiyanti

^1,2,†

,

Shian-Jang Yan

³,

Chih-Hsing Wu

^4,5,6

,

Ming-Jer Tang

^3,7,

Dar-Bin Shieh

^8,9,10,11,12,

Peter P. Liu

^13,14 and

Ping-Yen Liu

^1,15,*

¹

Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 70457, Taiwan

²

Department of Oral Biology, Faculty of Dentistry, Universitas Hang Tuah, Surabaya 60111, Indonesia

³

Department of Physiology, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan 70457, Taiwan

⁴

Department of Family Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70457, Taiwan

⁵

Department of Family Medicine, College of Medicine, National Cheng Kung University, Tainan 70457, Taiwan

⁶

Institute of Gerontology, College of Medicine, National Cheng Kung University, Tainan 70457, Taiwan

⁷

International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan 70457, Taiwan

⁸

Institute of Oral Medicine, National Cheng Kung University, Tainan 70101, Taiwan

⁹

Institute of Basic Medicine, National Cheng Kung University, Tainan 70101, Taiwan

¹⁰

Center of Applied Nanomedicine, National Cheng Kung University, Tainan 70101, Taiwan

¹¹

Core Facility Center, National Cheng Kung University, Tainan 701401, Taiwan

¹²

Department of Stomatology, National Cheng Kung University Hospital, Tainan 704302, Taiwan

¹³

Cardiac Function Laboratory, University of Ottawa Heart Institute, 40 Ruskin St., Ottawa, ON K1Y 4W7, Canada

¹⁴

Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1Y 4W7, Canada

¹⁵

Division of Cardiology, Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan

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^*

Author to whom correspondence should be addressed.

^†

These two authors contribute equally.

Int. J. Mol. Sci. 2021, 22(24), 13281; https://doi.org/10.3390/ijms222413281

Submission received: 26 September 2021 / Revised: 28 November 2021 / Accepted: 7 December 2021 / Published: 10 December 2021

(This article belongs to the Special Issue Rho Family Proteins and Their Regulators in Kidney Physiology and Pathology)

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Abstract

Chronic kidney disease (CKD) is normally related to proteinuria, a common finding in a compromised glomerular filtration barrier (GFB). GFB is a structure composed of glomerular endothelial cells, the basement membrane, and the podocytes. CKD with podocyte damage may be associated with actin cytoskeleton reorganization, resulting in podocyte effacement. Gelsolin plays a critical role in several diseases, including cardiovascular diseases and cancer. Our current study aimed to determine the connection between gelsolin and podocyte, and thus the mechanism underlying podocyte injury in CKD. Experiments were carried out on Drosophila to demonstrate whether gelsolin had a physiological role in maintaining podocyte. Furthermore, the survival rate of gelsolin-knocked down Drosophila larvae was extensively reduced after AgNO₃ exposure. Secondly, the in vitro podocytes treated with puromycin aminonucleoside (PAN) enhanced the gelsolin protein expression, as well as small GTPase RhoA and Rac1, which also regulated actin dynamic expression incrementally with the PAN concentrations. Thirdly, we further demonstrated in vivo that GSN was highly expressed inside the glomeruli with mitochondrial dysfunction in a CKD mouse model. Our findings suggest that an excess of gelsolin may contribute to podocytes damage in glomeruli.

Keywords: podocyte; gelsolin; actin; chronic kidney disease

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MDPI and ACS Style

Yu, C.-J.; Damaiyanti, D.W.; Yan, S.-J.; Wu, C.-H.; Tang, M.-J.; Shieh, D.-B.; Liu, P.P.; Liu, P.-Y. The Pathophysiologic Role of Gelsolin in Chronic Kidney Disease: Focus on Podocytes. Int. J. Mol. Sci. 2021, 22, 13281. https://doi.org/10.3390/ijms222413281

AMA Style

Yu C-J, Damaiyanti DW, Yan S-J, Wu C-H, Tang M-J, Shieh D-B, Liu PP, Liu P-Y. The Pathophysiologic Role of Gelsolin in Chronic Kidney Disease: Focus on Podocytes. International Journal of Molecular Sciences. 2021; 22(24):13281. https://doi.org/10.3390/ijms222413281

Chicago/Turabian Style

Yu, Chia-Jung, Dian W. Damaiyanti, Shian-Jang Yan, Chih-Hsing Wu, Ming-Jer Tang, Dar-Bin Shieh, Peter P. Liu, and Ping-Yen Liu. 2021. "The Pathophysiologic Role of Gelsolin in Chronic Kidney Disease: Focus on Podocytes" International Journal of Molecular Sciences 22, no. 24: 13281. https://doi.org/10.3390/ijms222413281

APA Style

Yu, C.-J., Damaiyanti, D. W., Yan, S.-J., Wu, C.-H., Tang, M.-J., Shieh, D.-B., Liu, P. P., & Liu, P.-Y. (2021). The Pathophysiologic Role of Gelsolin in Chronic Kidney Disease: Focus on Podocytes. International Journal of Molecular Sciences, 22(24), 13281. https://doi.org/10.3390/ijms222413281

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The Pathophysiologic Role of Gelsolin in Chronic Kidney Disease: Focus on Podocytes

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