title: Kidney growth during catabolic illness: what it does not destroy makes it grow stronger.
abstract: The kidney undergoes hypertrophy under conditions that paradoxically cause a loss of lean body mass, such as diabetes, acidosis, and chronic kidney disease. What unique mechanisms account for kidney growth during negative nitrogen balance? One adaptation is that renal tubular cells substantially decrease protein breakdown during kidney cell growth. In this review, we discuss how acidosis and diabetes reduce protein breakdown within the kidney and the intracellular signaling pathways that may regulate protein metabolism. Our results suggest that in cell culture models and in acute diabetes, kidney cells specifically reduce protein breakdown by the lysosomal pathway of chaperone-mediated autophagy. This differs from the activation of proteolysis by the ubiquitin-proteasome system in muscle in acute diabetes and uremia. A shared signaling pathway regulates protein breakdown in both kidney and skeletal muscle, namely, phosphatidylinositol-3 kinase signaling. Diabetes mellitus activates signaling through this pathway in the kidney while down-regulating it in skeletal muscle. We conclude that similar signaling pathways may regulate distinct proteolytic pathways in different tissues.
authors.affiliation: Research Service, Atlanta Department of Veterans Affairs Medical Center, Decatur, Georgia. hfranch@emory.edu <hfranch@emory.edu>
authors.forename: Harold A
authors.initials: HA
authors.lastname: Franch
mesh_terms: D000138:Acidosis / Q000378:metabolism; D001343:Autophagy; D003920:Diabetes Mellitus / Q000378:metabolism; D006801:Humans; D006984:Hypertrophy; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D007674:Kidney Diseases / Q000378:metabolism / Q000503:physiopathology*; D008660:Metabolism; D018832:Molecular Chaperones / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014511:Uremia / Q000378:metabolism
chemical_list: D018832:Molecular Chaperones; D011506:Proteins; D019869:Phosphatidylinositol 3-Kinases