AUTHOR=Cao Shi-Lu , Luo Hong-Yan , Gao Yong-Cai , Lan Xiao-Mei , Liu Shun-Yao , Li Bo , Bao Li , E. Jing , Ma Danna , Zhang Guo-Qing , Yang Li-Rong , Bao Xi , Zheng Ya-Li TITLE=TFP5-Mediated CDK5 Activity Inhibition Improves Diabetic Nephropathy via NGF/Sirt1 Regulating Axis JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=10 YEAR=2022 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.829067 DOI=10.3389/fcell.2022.829067 ISSN=2296-634X ABSTRACT=
Diabetic nephropathy (DN) is one of the leading causes of chronic kidney disease (CKD), during which hyperglycemia is composed of the major force for the deterioration to end-stage renal disease (ESRD). However, the underlying mechanism triggering the effect of hyperglycemia on DN is not very clear and the clinically available drug for hyperglycemia-induced DN is in need of urgent development. Here, we found that high glucose (HG) increased the activity of cyclin-dependent kinase 5 (CDK5) dependent on P35/25 and which upregulated the oxidative stress and apoptosis of mouse podocytes (MPC-5). TFP5, a 25-amino acid peptide inhibiting CDK5 activity, decreased the secretion of inflammation cytokines in serum and kidney, and effectively protected the kidney function in