Role of TFEB in regulation of the podocyte actin cytoskeleton

Cuili Li; Yan Yang; Luan Li; Yingwen Chen; Qingying Shi; Hong Zhang; Li Zhang; Yuanhan Chen; Ruizhao Li; Zhilian Li; Shuangxin Liu; Zhiming Ye; Xingchen Zhao; Xinling Liang

doi:10.1016/j.abb.2023.109752

Role of TFEB in regulation of the podocyte actin cytoskeleton

Arch Biochem Biophys. 2023 Oct 1:747:109752. doi: 10.1016/j.abb.2023.109752. Epub 2023 Sep 13.

Authors

Cuili Li¹, Yan Yang², Luan Li¹, Yingwen Chen¹, Qingying Shi², Hong Zhang¹, Li Zhang³, Yuanhan Chen³, Ruizhao Li³, Zhilian Li³, Shuangxin Liu³, Zhiming Ye³, Xingchen Zhao⁴, Xinling Liang⁵

Affiliations

¹ School of Medicine, South China University of Technology, Guangzhou, 510006, China; Department of Nephrology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
² Department of Nephrology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China.
³ Department of Nephrology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
⁴ Department of Nephrology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China. Electronic address: zhaoxingchen@gdph.org.cn.
⁵ School of Medicine, South China University of Technology, Guangzhou, 510006, China; Department of Nephrology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China. Electronic address: liangxinling@gdph.org.cn.

PMID: 37714254
DOI: 10.1016/j.abb.2023.109752

Abstract

Podocyte injury is linked to the pathogenesis and progression of renal disease. The Transcription Factor EB (TFEB), a master regulator of the autophagy and lysosomal pathways, has been found to exert cell- and tissue-specific biological function. To explore TFEB function and underlying mechanisms in podocytes, a total of 4645 differentially expressed genes (DEGs) were detected in TFEB-knockdown mouse podocytes by transcriptome sequencing. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Ingenuity Pathway Analysis showed that, apart from the enrichment in autophagy and lysosomal pathways, DEGs were enriched in cytoskeleton structure (Actin Cytoskeleton, Focal Adhesion, and Adherens Junction), as well as cytoskeleton regulatory molecular signaling (Hippo and Rho GTPase Signaling). In vitro, TFEB knockdown resulted in podocyte cytoskeletal rearrangement, which was disorganized with cortical distribution of actin filaments. Further, TFEB knockdown decreased mRNA and protein levels of Synaptopodin and led to the rearrangement of Synaptopodin. Inhibition of TFEB decreased mRNA levels for proteins involved in actin cytoskeleton dynamics. Moreover, apoptosis was increased by TFEB knockdown in podocyte. In summary, this study initiated a comprehensive analysis of the role of TFEB in podocyte function and the potential underlying mechanisms, and identified a novel role for TFEB in regulation of the podocyte actin cytoskeleton.

Keywords: Bioinformatics analysis; Cytoskeleton; Podocytes; Transcription factor EB; Transcriptome sequencing.