title: Upregulation of podocyte-secreted angiopoietin-like-4 in diabetic nephropathy.
abstract: Podocyte injury plays a key role in the development of diabetic nephropathy (DN). Understanding the changes in podocyte structure and function in diabetes mellitus may lead to novel diagnostic tools and treatment strategies for DN. Albuminuria, histological alterations, and podocyte injury were detected at different time points in streptozotocin (STZ)-induced diabetic rats. Increased urinary albumin-to-creatinine ratios (ACR) and podocyte injury were significantly observed 4 weeks post-STZ injection. We determined the glomerular expression and distribution of angiopoietin-like 4 (Angptl4) by immunofluorescence and real-time PCR. Glomerular Angptl4 expression was mostly colocalized with synaptopodin, a podocyte marker, with substantial additional overlap with the glomerular basement membrane (GBM). This finding indicated that Angptl4 might be primarily secreted by podocytes and moved toward the GBM. Moreover, we observed by Western blot analysis and ELISA that the urinary Angptl4 level was gradually upregulated in both STZ-induced rats and diabetic patients with microalbuminuria and macroalbuminuria. We further found that the increased glomerular Angptl4 expression was closely related to the urinary ACR level and podocyte injury. In addition, the urinary Angptl4 expression was closely associated with albuminuria in the rats and patients with DN. This study is the first to show that podocyte-secreted Angptl4 is upregulated in DN and can be detected in urine. Angptl4 might function as a podocyte injury marker and could be a potential and novel diagnostic and therapeutic biomarker for DN.
authors.affiliation: Department of Nephrology, 2nd Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Jian-Si
authors.initials: JS
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Peng
authors.forename: Shi-Yao
authors.initials: SY
authors.lastname: Wei
authors.forename: Shi-Lei
authors.initials: SL
authors.lastname: Zhao
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Zhu
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: He
authors.forename: Qiu-Ju
authors.initials: QJ
authors.lastname: Wei
authors.forename: Bing
authors.initials: B
authors.lastname: Li
mesh_terms: D000419:Albuminuria / Q000378:metabolism*; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000378:metabolism*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism*; D050533:Glomerular Basement Membrane / Q000378:metabolism*; D006801:Humans; D008297:Male; D008840:Microfilament Proteins; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000633:toxicity; D015854:Up-Regulation
chemical_list: C528241:ANGPTL4 protein, rat; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D000903:Antibiotics, Antineoplastic; D008840:Microfilament Proteins; C503969:Synpo protein, rat; D013311:Streptozocin