c-Src is in the effector pathway linking uPAR and podocyte injury

• Published in: The Journal of clinical investigation Vol. 129; no. 5; pp. 1827 - 1829
• Main Authors: Kopp, Jeffrey B., Heymann, Jurgen
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.05.2019
• Subjects: Animal genetic engineering; Animals; Biomedical research; Biopsy; Bone marrow; Epigenetics; Fibrinolytic agents; Gene expression; Genetic aspects; Genetic engineering; Glomerulosclerosis, Focal Segmental; Immune system; Innate immunity; Integrins; Kidney Diseases; Kidneys; Kinases; Laboratory rats; Mice; Novels; Oxidative stress; Phosphorylation; Physiology; Plasmin; Podocytes; Protein Isoforms; Proteins; Proteinuria; Receptors, Urokinase Plasminogen Activator; Ribonucleic acid; RNA; Src protein; Transgenic animals; Transgenic mice; U-Plasminogen activator
• ISSN: 0021-9738; 1558-8238; 1558-8238
• DOI: 10.1172/JCI127927

The role of urokinase-type plasminogen activator receptor (uPAR) in kidney physiology and pathology has attracted considerable attention. The protein uPAR has dual functions: as a key regulator of plasmin generation and a component of the innate immune system. In the current issue, Wei and colleagues describe a transgenic mouse expressing Plaur RNA in glomerular podocytes. The mice manifested podocyte injury, including c-Src phosphorylation, proteinuria, and focal segmental glomerulosclerosis (FSGS). Plaur-transgenic mice on a β3 integrin-deficient background were protected from podocyte injury. Renal biopsies from subjects with FSGS, but not those with other glomerular diseases, manifested increased c-Src phosphorylation in podocytes. These findings suggest a novel injury mechanism in FSGS, with possible implications for new treatment strategies.