Chinese scientists reveal target YY1 could treat diabetic nephropathy

The conversion growth factor beta 1 (TGF beta 1, encoded by the gene TGFB1) has been identified as the main causative factor for diabetic nephropathyHowever, the current strategy of antagonistic TGF beta 1 has not shown beneficial therapeutic results in clinical trialsIn a new study, researchers from research institutions such as Shanghai Jiaotong University and Fudan University in China have devised a mass spectrometry-based DNA-protein interaction screening method to identify transcriptional inhibitors that bind to TGFB1 promotersThey identified a protein molecule called Yin yang 1 (Yin Yang 1, YY1) as a powerful TGFB1 inhibitorThe findings are published in the September 18, 2019 issue of science Translational Medicine with the title "Yin Yang 1 protein ameliorates diabetic nephropathyy, throughional repression of TGF beta1"YY1 binds directly to the TGFB1 promoter region and inhibits the transcription of TGFB1 in human glomerular membrane cellsIn mouse models, YY1 levels in the membrane cells of the glomerular membrane increased during early diabetic nephrite lesions and decreased during later diabetic kidney lesionsInhibition of YY1 expression in the kidneys can increase glomerular sclerosis, while YY1 overexpression in the kidneys weakens glomerular sclerosisin addition, although patients with higher YY1 expression and patients with lower YY1 expression had similar diabetes progression, patients with higher YY1 expression developed diabetic nephropathy more slowly than those with lower YY1 expressionthe researchers found that a small molecule called eudesmin inhibited TGF beta 1 and other fibrosis factors by increasing YY1 expression in human glomerular membrane cells, and reduced diabetic kidney lesions in mouse models of diabetic nephropathy by increasing YY1 expressionthese results suggest that YY1 is a powerful TGFB1 transcription inhibitor in diabetic mice, and that small molecules targeted at YY1 may be a promising treatment for diabetic nephropathyReferences: Pan Gao et alYin Yang 1 protein ameliorates diabetic nephropathy pathology over-the-mailion al-repression of TGF beta 1Science Translational Medicine, 2019, doi:10.1126/scitranslmed.aaw2050.