Hydroxysafflor Yellow A Ameliorates Renal Fibrosis by Suppressing TGF-β1-Induced Epithelial-to-Mesenchymal Transition

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.

ROS induces epithelial‑mesenchymal transition via the TGF‑β1/PI3K/Akt/mTOR pathway in diabetic nephropathy

“…HG induces the EMT via an ROS-mediated mechanism in NRK-52E cells. EMT of tubular epithelial cells is the leading cause of kidney fibrosis (5). To investigate whether EMT is induced by ROS, TGF-β1 and the PI3K/Akt/mTOR signalling pathway, morphological changes of NRK-52E cells were assessed under a microscope.…”

Hydroxysafflor Yellow A Alleviates Ovalbumin-Induced Asthma in a Guinea Pig Model by Attenuateing the Expression of Inflammatory Cytokines and Signal Transduction

“…These characteristic of HSYA may be beneficial for the treatment of early sensitization and late injury in asthma. Besides, HSYA attenuated pulmonary fibrogenesis induced by BLM in mice (Jin et al, 2016b), and inhibited TGF-β1 signal transduction (Hu et al, 2016). Because TGF-β1 is a key cytokine of the important pathological mechanisms in airway remodeling, thus HSYA may be beneficial for the treatment of airway remodeling in asthma.…”

Hydroxysafflor Yellow A: A Promising Therapeutic Agent for a Broad Spectrum of Diseases

“…HSYA had protective effect against fibrosis in renal cells, through inhibiting TGF- β 1/Smad3-mediated epithelial-mesenchymal transition signaling pathway [ 109 ]. Topical use of HSYA could relieve the UV-induced skin damage in mice by promoting recovery from stretching, inhibiting epidermal hyperproliferation and keeping the structural integrity of the skin via antioxidative activity [ 110 ].…”