title: Targeted proteomics of isolated glomeruli from the kidneys of diabetic rats: sorbin and SH3 domain containing 2 is a novel protein associated with diabetic nephropathy.
abstract: To evaluate proteins associated with the development of diabetic nephropathy, a major cause of the end-stage renal disease, we analyzed protein expression in isolated glomeruli from spontaneous type 2 diabetic (OLETF) rats and their age-matched control littermates (LETO) in the early and proteinuric stages of diabetic nephropathy using QSTAR Elite LC-MS/MS. Among the 191 and 218 proteins that were altered significantly in the OLETF rats, twenty-four were actin cytoskeleton-associated proteins implicated in the formation of stress fibers, and the impairment of actin polymerization, intermediate filaments and microtubules. Importantly, sorbin and SH3 domain containing 2 (SORBS2), which is involved in the formation of stress fibers, was significantly upregulated in both stages of diabetic nephropathy (1.49- and 1.97-fold, resp.). Immunohistochemical and quantitative-PCR analyses revealed upregulation of SORBS2 in podocytes of glomeruli of OLETF rats. Our findings suggested that SORBS2 may be associated with the development of diabetic nephropathy possibility by reorganization of actin filaments.
authors: Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors: Shinya
authors: S
authors: Nakatani
authors: Anna
authors: A
authors: Kakehashi
authors: Eiji
authors: E
authors: Ishimura
authors: Shotaro
authors: S
authors: Yamano
authors: Katsuhito
authors: K
authors: Mori
authors: Min
authors: M
authors: Wei
authors: Masaaki
authors: M
authors: Inaba
authors: Hideki
authors: H
authors: Wanibuchi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000652:urine; D018450:Disease Progression; D015536:Down-Regulation; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000648:ultrastructure; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism / Q000648:ultrastructure; D011507:Proteinuria / Q000209:etiology; D040901:Proteomics / Q000379:methods*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020334:Rats, Inbred OLETF; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008840:Microfilament Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; C490754:Sorbs2 protein, rat