Abstract
ObjectiveRenal fibrosis is the common pathological foundation of many chronic kidney diseases (CKDs). The aim of this study was to investigate whether Hydroxysafflor yellow A (HSYA) can preserve renal function by inhibiting the progression of renal fibrosis and the potential mechanisms.MethodsRenal fibrosis was induced by unilateral ureteral obstruction (UUO) performed on 7-week-old C57BL/6 mice. HSYA (10, 50 and 100 mg/kg) were intragastrically administered. Sham group and model group were administered with the same volume of vehicle. Serum and kidney samples were collected 14 days after the UUO surgery. Serum biochemical indicators were measured by automatic biochemical analyzer. Histological changes were evaluated by HE and Masson staining. In vitro, the anti-fibrotic effect of HSYA was tested on human recombinant transforming growth factor-β1 (TGF-β1) stimulated HK-2 cells. The protein levels of α-SMA, collagen-I and fibronectin in kidney tissue andHK-2 cells were measured by immunohistochemistry and immunofluorescence. The protein levels of apoptosis-relative and TGF-β1/Smad3 signaling were detected by western blot.ResultsHSYA slowed the development of renal fibrosis both in vivo and in vitro. In UUO rats, renal function index suggested that HSYA treatment decreased the level of serum creatinine (Scr) and blood urea nitrogen (BUN) rose by UUO (P<0.05). HE staining and Masson staining demonstrated that kidney interstitial fibrosis, tubular atrophy, and inflammatory cell infiltration were notably attenuated in the high-dose HSYA group compared with the model group. The expressions of α-SMA, collagen-I and fibronectin were decreased in the UUO kidney and HK-2 cells of the HSYA-treatment group. Moreover, HSYA reduced the apoptotic rate of HK-2 cells stimulated by TGF-β1. Further study revealed that HSYA regulated the TGF-β1/Smads signaling pathway both in kidney tissue and HK-2 cells.ConclusionsThese results suggested that HSYA had a protective effect against fibrosis in renal cells, at least partly, through inhibiting TGF-β1/smad3-mediated Epithelial–mesenchymal transition signaling pathway.
Highlights
Chronic kidney disease (CKD) is an increasing public health issue with up to 160 million individuals worldwide predicted to be affected by 2020 [1, 2]
In ureteral obstruction (UUO) rats, renal function index suggested that Hydroxysafflor yellow A (HSYA) treatment decreased the level of serum creatinine (Scr) and blood urea nitrogen (BUN) rose by UUO (P
Further study revealed that HSYA regulated the transforming growth factor-β1 (TGF-β1)/Smads signaling pathway both in kidney tissue and HK-2 cells. These results suggested that HSYA had a protective effect against fibrosis in renal cells, at least partly, through inhibiting TGF-β1/smad3-mediated Epithelial–mesenchymal transition signaling pathway
Summary
Chronic kidney disease (CKD) is an increasing public health issue with up to 160 million individuals worldwide predicted to be affected by 2020 [1, 2]. Though the specific mechanism of CKD remains uncertain, renal fibrosis, tubulointerstitial fibrosis is accepted asthe common pathway for chronic kidney disease leading to end-stage renal failure, regardless of etiology[3].Renal fibrogenesis is a dynamic and converging process, characterized by activated tubulointerstitial myofibroblast and the production of excessive extracellular matrix (ECM), and the activated myofibroblasts is believed to be a main contributor in the pathogenesis of renal interstitial fibrosis [4, 5]. The exact origins of these myofibroblasts remain uncertain, emerging evidence suggests that they may originated from EMT [6]. Studies confirmed that EMT regulated by numerous cytokines, and TGF-β1 is considered the major regulator
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