Scientists find new target to treat chronic kidney disease

Renal fibrosis is a common pathophysiological change of chronic kidney disease. It can lead to renal failure, and there is no better treatment. Dr. Ian Logan from the University of Newcastle, UK, and his colleagues conducted a study of epigenetic modulators through recombinant human proteins, including SETD7, to determine whether epigenetically modulating factors are potential therapeutic targets for chronic kidney disease. The results were published in the Lancet.

The researchers used human kidney fibroblasts, mesangial cells, and mouse embryonic fibroblasts to analyze fibroblast transformation, extracellular matrix protein expression (immunofluorescence, wound healing), and whole-gene expression (whole genome chip technology) levels. The interaction of the lysine methyltransferase SETD7 with SMAD3 (immunoprecipitation), SMAD3 stability, and SMAD3 nuclear import was analyzed using renal tubular epithelial cells.

The results show that Transforming growth factor β1 (TGFβ1) -induced myofibroblast transformation was not found in SETD7-deficient cells. In addition, SETD7 lacks fibroblast collagen concentration and fibronectin - 1 concentration was lower than SETD7 normal cells, and wound healing slowed down. TGFβ1 can promote the interaction of SMAD3 with SETD7, thus increasing the stability of SMAD3 in cells. Immunofluorescence and subcellular separation revealed that SMAD3 nuclear input was dependent on SETD7. SETD7 overexpression increased the SMAD3 transcriptional activity of cis-regulatory elements (plasminogen activator inhibitor 1 and CAGA), while SETD7 deficiency can reduce SMAD3 transcriptional activity. Gene Ontology analysis showed that SETD7 regulates the expression of fibrogenic genes.

The study shows that SETD7 plays an important role in fibrogenesis - a major feature of chronic kidney disease and other fibrotic diseases. In view of the results of this study, drug inhibition of epigenetic regulators is expected to be a novel therapeutic approach for chronic kidney disease. Flarebio offers recombinant proteins of good quality such as recombinant ECE1 at competitive prices.