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The Use of Targeted Next Generation Sequencing to Explore Candidate Regulators of TGF-β1's Impact on Kidney Cells. | LitMetric

The Use of Targeted Next Generation Sequencing to Explore Candidate Regulators of TGF-β1's Impact on Kidney Cells.

Front Physiol

Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.

Published: December 2018

AI Article Synopsis

  • - The study investigates the role of Transforming Growth Factor-beta (TGF-β1) in chronic kidney failure and its effects on mesangial cells, which are crucial in diabetic nephropathy progression.
  • - Researchers treated mesangial cells with TGF-β1 and used advanced next-generation sequencing to analyze changes in RNA, microRNA, and DNA methylation, resulting in a comprehensive understanding of the regulatory effects at a molecular level.
  • - Findings indicate that specific genes (KLF7 and Gja4) are linked to TGF-β1-regulated DNA methylation and highlight the connection between epigenetic alterations and gene expression related to kidney disease, paving the way for further research into therapeutic targets.

Article Abstract

Transforming growth factor-beta (TGF-β1) plays an important regulatory role in the progression of chronic kidney failure. Further, damage to kidney glomerular mesangial cells is central to the progression of diabetic nephropathy. The aim of this study was to explore the genetic associations between mRNA, microRNA, and epigenetics in mesangial cells in response to TGF-β1. The regulatory effects of TGF-β1 on mesangial cells were investigated at different molecular levels by treating mesangial cells with TGF-β1 for 3 days followed by genome-wide miRNA, RNA, DNA methylation, and H3K27me3 expression profiling using next generation sequencing (NGS). Our results provide the first comprehensive, computationally integrated report of RNA-Seq, miRNA-Seq, and epigenomic analyses across all genetic variations, confirming the occurrence of DNA methylation and H3K27me3 in response to TGF-β1. Our findings show that the expression of KLF7 and Gja4 are involved in TGF-β1 regulated DNA methylation. Our data also provide evidence of the association between epigenetic changes and the expression of genes closely related to TGF-β1 regulation. This study has advanced our current knowledge of mechanisms that contribute to the expression of TGF-β1-regulated genes involved in the pathogenesis of kidney disease. The molecular underpinnings of TGF-β1 stimulation of kidney cells was determined, thereby providing a robust platform for further target exploration.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295563PMC
http://dx.doi.org/10.3389/fphys.2018.01755DOI Listing

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