title: Emerging role of podocyte autophagy in the progression of diabetic nephropathy.
abstract: Glomerular podocytes are pivotal in maintaining glomerular filtration barrier function. As severe podocyte injury results in proteinuria in patients with diabetic nephropathy, determining the pathogenesis of podocyte injury may contribute to the development of new treatments. We recently showed that autophagy is involved in the pathogenesis of diabetes-related podocyte injury. Insufficient podocyte autophagy and podocyte loss are observed in diabetic patients with massive proteinuria. Podocyte loss and massive proteinuria occur in high-fat diet-induced diabetic mice with podocyte-specific autophagy deficiency, with podocytes of these mice and of diabetic rats having huge damaged lysosomes. Sera from diabetic patients and from rodents with massive proteinuria cause autophagy insufficiency, resulting in lysosome dysfunction and apoptosis of cultured podocytes. These findings suggest the importance of autophagy in maintaining lysosome homeostasis in podocytes under diabetic conditions. Impaired autophagy may be involved in the pathogenesis of podocyte loss, leading to massive proteinuria in diabetic nephropathy.
authors.affiliation: a Department of Medicine ; Shiga University of Medical Science ; Otsu; Shiga , Japan.
authors.forename: Mako
authors.initials: M
authors.lastname: Yasuda-Yamahara
authors.affiliation: a Department of Medicine ; Shiga University of Medical Science ; Otsu; Shiga , Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kume
authors.affiliation: a Department of Medicine ; Shiga University of Medical Science ; Otsu; Shiga , Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Tagawa
authors.affiliation: a Department of Medicine ; Shiga University of Medical Science ; Otsu; Shiga , Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maegawa
authors.affiliation: a Department of Medicine ; Shiga University of Medical Science ; Otsu; Shiga , Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Uzu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism*; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D050199:Podocytes / Q000378:metabolism*; D011507:Proteinuria / Q000378:metabolism*
keywords: MTORC1; autophagy; diabetic nephropathy; lysosome; podocyte injury; proteinuria