Mutation of regulatory phosphorylation sites in PFKFB2 worsens renal fibrosis
Mardiana Lee, Geoff Harley, Marina Katerelos, Kurt Gleich, Mitchell A Sullivan, Adrienne Laskowski, Melinda Coughlan, Scott A Fraser, Peter F Mount, David A Power
Scientific Reports | NATURE RESEARCH | Published : 2020
Fatty acid oxidation is the major energy pathway used by the kidney, although glycolysis becomes more important in the low oxygen environment of the medulla. Fatty acid oxidation appears to be reduced in renal fibrosis, and drugs that reverse this improve fibrosis. Expression of glycolytic genes is more variable, but some studies have shown that inhibiting glycolysis reduces renal fibrosis. To address the role of glycolysis in renal fibrosis, we have used a genetic approach. The crucial control point in the rate of glycolysis is 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase. Phosphorylation of the kidney isoform, PFKFB2, on residues Ser468 and Ser485 stimulates glycolysis and is the mo..View full abstract
This work was supported by an NHMRC Project Grant to D.A.P. and P.F.M. M.L. was supported by a NHMRC Postgraduate Scholarship and a Jacquot top-up grant from the Royal Australasian College of Physicians. G.H. was supported by a Postgraduate Scholarship from the University of Melbourne. The Austin Medical Research Foundation and the Research Special Purposes Fund of the Department of Nephrology at Austin Health also provided supporting funds. We acknowledge the laboratory of Prof Bruce Kemp at St. Vincent's Institute of Medical Research who maintained the PFKFB2 KI transgenic line for a period. We gratefully acknowledge the assistance of the Microscopy Unit of Florey Institue of Neuroscience and Mental Health. Parts of this study were presented at the American Socisty of Nephrology Annual Meeting in 2019.