Lysophosphatidic acid increases mesangial cell proliferation in models of diabetic nephropathy via Rac1/MAPK/KLF5 signaling

Abstract

Kidney disease: Mechanisms of diabetes-related damage A potent molecular mediator of diabetic kidney disease induces its pathogenic effects via proteins that could be targeted with future drug therapies. Yoon Sin Oh from Eulji University in Seongnam-si and Hee-Sook Jun from Gachon University in Incheon, both in South Korea, and colleagues treated certain cells found in the kidney’s glomerulus, the organ’s filtering unit, with a signaling molecule called lysophosphatidic acid (LPA) that is elevated in the blood of diabetic mice. They showed that LPA stimulated cellular proliferation and boosted the expression of proteins involved in regulating the cell cycle and a multipurpose signaling pathway. They then inhibited the activity of these proteins to prevent the kidney cells’ hyperproliferation, both in cell culture and in diabetic mice. The results highlight the potential of blocking mediators of LPA signaling to treat kidney-related complications of diabetes.