RGED RGED / Novel players in renal fibrosis uncovered by gene expression analyses of TGF-1 treated renal tubular epithelial cells and diseased kidneys

Public on 2022-06-30

Description

Tubular epithelial cells (TECs) play a major role in potentiating renal fibrosis. While TGF-1 is a key inducer of the pro-fibrotic phenotype in TECs, inhibition of TGF-1 also blocks its protective effects, making this an unsuccessful strategy for treating renal fibrosis. Molecules induced by TGF-1 to regulate TEC phenotype would serve as more specific and effective targets.; To uncover such molecules, we performed high throughput analyses on TGF-1 treated renal tubular epithelial cells (HKC). RNA sequencing identified 3565 genes and proteomics identified 74 proteins differentially regulated by TGF-1 in HKC. We then selected 47 genes that were most upregulated in our in vitro datasets and that do not have well-characterized roles in renal fibrosis based on our review of the literature.; We searched 8 publicly available datasets containing transcriptomic data from diseased human kidneys for gene expression patterns of the selected genes and found that MARCKS and DOCK2 were amongst the most consistently upregulated in the human datasets.; In HKC, MARCKS knockdown decreased TGF-1 mediated upregulation of pro-fibrotic markers, while DOCK2 knockdown had the opposite effect. Our data suggests novel roles for these proteins in renal TECs as potential promoters the pro-fibrotic phenotype.

Overall Design

Gene expression analysis of RNA sequencing data from HKC treated with vehicle vs. TGF-1.

Curator

yq_pan

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