title: Propyl gallate plays a nephroprotective role in early stage of diabetic nephropathy associated with suppression of glomerular endothelial cell proliferation and angiogenesis.
abstract: There is growing evidence suggesting that glomerular endothelial cell proliferation and angiogenesis may be responsible for the pathophysiological events in the early stage of diabetic nephropathy. This study was designed to investigate the factors related to glomerular endothelial cell proliferation and glomerular angiogenesis and assess the effect of propyl gallate on preventing these disorders in diabetic rats. We found that glomerular hypertrophy, glomerular mesangial matrix expansion, and albuminuria were significantly increased in DN rats. CD31+ endothelial cells significantly increased in glomerulus of diabetic rats. Double immunofluorescence staining showed some structurally defective vasculus tubes in glomerulus. Real-time PCR and western blot demonstrated the glomerular eNOS expression remained at the same level, while remarkable decreased NO productions and suppressed eNOS activities were observed in diabetic rats. Treatment with propyl gallate improved glomerular pathological changes, reduced endothelial cell proliferation, decreased albuminuria, and restored eNOS activity, but did not alter eNOS expression. These data suggest that endothelial cell proliferation and immature angiogenesis may be the contributors to progression of DN. Propyl gallate is a potential novel therapeutic agent on prevention of diabetic nephropathy.
authors.affiliation: Department of Nephrology, Renmin Hospital, Hubei University of Medicine, Hubei, Shiyan 442000, China. shaojiangt@yahoo.com.cn
authors.forename: Shaojiang
authors.initials: S
authors.lastname: Tian
authors.forename: Junming
authors.initials: J
authors.lastname: Tang
authors.forename: Huihui
authors.initials: H
authors.lastname: Liu
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.forename: Jianming
authors.initials: J
authors.lastname: Shen
authors.forename: Junfeng
authors.initials: J
authors.lastname: Li
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Gan
mesh_terms: D000419:Albuminuria / Q000209:etiology / Q000517:prevention & control; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006984:Hypertrophy; D007274:Injections, Intraperitoneal; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D058990:Molecular Targeted Therapy; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011435:Propyl Gallate / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats
chemical_list: D020533:Angiogenesis Inhibitors; D000975:Antioxidants; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D009569:Nitric Oxide; D011435:Propyl Gallate; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat