title: H2S improves renal fibrosis in STZ-induced diabetic rats by ameliorating TGF-β1 expression.
abstract: Nephropathy develops in many patients with type 1 diabetes mellitus (T1DM). However, the specific mechanisms and therapies remain unclear. For this purpose we investigated the effects of hydrogen sulfide (H2S) on renal fibrosis in streptozotocin (STZ) induced diabetic rats and its underlying mechanisms. Experimental rats were randomly divided into four groups: Control group (normal rats), DM group (diabetes rats), DM + NaHS group [diabetes rats treated with sodium hydrosulfide (NaHS)], and NaHS group (normal rats treated with NaHS). The diabetic models were established by intraperitoneal injection of STZ. The NaHS-treated rats were injected with NaHS as an exogenous donor of H2S. At the same time, control group and DM group were administrated with equal doses of normal saline (NS). After eight weeks, the rats' urine samples were collected to measure the renal hydroxyproline content by basic hydrolysis method with a hydroxyproline detection kit. Collagen I and III content was detected by immunohistochemical method, and the pathology morphology of kidney was analyzed by Masson staining. Protein expressions of transforming growth factor beta 1 (TGF-β1), ERK1/2, TIMP1, TIMP2, MMP-2, MMP-7, MMP-8, MMP-11, and MMP-14 were assessed by western blotting. The results showed that significant fibrosis occurred in the kidney of diabetes rats. NaHS treatment downregulated TGF-β1, ERK1/2, TIMP1, TIMP2, MMP-2, MMP-7, MMP-8, MMP-11, and MMP-14 expressions in the kidney of these diabetes rats (p<.01). This result suggests that NaHS treatment could attenuate renal fibrosis by TGF-β1 signaling, and its mechanisms may be correlated with ERK1/2 expression and modulation of MMPs/TIMPs expression. Therefore, H2S may provide a promising option for defensing against diabetic renal fibrosis through TGF-β1 signaling, equilibrating the balance between profibrotic and antifibrotic mediators.
authors.affiliation: a Cardiovascular Department , The First Affiliated Hospital of the University of South China , Hengyang , Hunan , PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: a Cardiovascular Department , The First Affiliated Hospital of the University of South China , Hengyang , Hunan , PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: a Cardiovascular Department , The First Affiliated Hospital of the University of South China , Hengyang , Hunan , PR China.
authors.forename: Ou
authors.initials: O
authors.lastname: Zeng
authors.affiliation: a Cardiovascular Department , The First Affiliated Hospital of the University of South China , Hengyang , Hunan , PR China.
authors.forename: Jun Mao
authors.initials: JM
authors.lastname: Liu
authors.affiliation: a Cardiovascular Department , The First Affiliated Hospital of the University of South China , Hengyang , Hunan , PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications; D003928:Diabetic Nephropathies / Q000209:etiology / Q000517:prevention & control*; D005355:Fibrosis; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007668:Kidney / Q000473:pathology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013311:Streptozocin; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; C508962:Tgfb1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D013311:Streptozocin; D020782:Matrix Metalloproteinases; D006862:Hydrogen Sulfide
keywords: Hydrogen sulfide; diabetic renal fibrosis; extracellular signal-regulated kinase-1/2; matrix metalloproteinases/tissue inhibitors of metalloproteinases; transforming growth factor beta 1