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.

Protection of Curcumin against Streptozocin-Induced Pancreatic Cell Destruction in T2D Rats

“…The type 2 DM rat model was established as previously described [27,28]. Briefly, Sprague-Dawley rats (190-210 g) were randomly divided into four groups: control group (n = 12), T2D group (n = 12), T2D + PBS group (n = 12), and T2D + Cur group (n = 12).…”

Matrix Metalloproteinases-7 and Kidney Fibrosis

“…Recent studies have revealed the existence of a close relationship between MMP-7 and TGF-β signaling (Figure 2 ). Li et al ( 2017 ) observed that the expression of TGF-β1 and MMP-7 are upregulated in STZ-induced diabetic nephropathy rats but markedly decreased in diabetic nephropathy rats treated with sodium hydrosulfide (Li et al, 2017 ), which suggests regulation between TGF-β and MMP-7. MMP-7 is also closely related to TGF-β/Smad4 signaling (Xiao et al, 2016 ).…”

Hydrogen Sulfide Alleviates Skeletal Muscle Fibrosis via Attenuating Inflammation and Oxidative Stress

“…The results of this study showed that MMP-1, MMP-2, MMP-9, and MMP-14 were significantly increased in mice in the contusion group, while the H 2 S treatment group had decreased mRNA levels of MMPs (MMP-1, MMP-2, MMP-9, and MMP-14) compared with the contusion group (Figure 7). In models of diabetes-induced kidney injury (Li et al, 2017) and myocardial fibrosis (Xiao et al, 2015), H 2 S reduced kidney injury and myocardial fibrosis by lowering the levels of MMPs. In addition, MMPs are significantly up-regulated in the dystrophic muscle of mdx mice, and the absence or inhibition of MMPs can significantly improve muscle structure and function, and reduce muscle fibrous necrosis in MDX mice (Kumar et al, 2010;Hindi et al, 2013).…”