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Role of TFEB in regulation of the podocyte actin cytoskeleton
Ist Teil von
Archives of biochemistry and biophysics, 2023-10, Vol.747, p.109752-109752, Article 109752
Ort / Verlag
Elsevier Inc
Erscheinungsjahr
2023
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
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.
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•Cytoskeleton structure and its regulatory signaling were enriched in TFEB-knockdown podocytes by GO, KEGG and IPA analysis.•TFEB knockdown resulted in podocyte cytoskeletal rearrangement.•TFEB knockdown decreased mRNA levels of proteins involved in actin cytoskeleton dynamics.