Yongheng Bai1, Hong Lu2, Ge Zhang3, Cunzao Wu4, Chengcheng Lin1, Yong Liang1, Bicheng Chen5. 1. Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, China. 2. Department of Laboratory Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, China. 3. Department of Orthopedics, People's Hospital of Luzhou City, Luzhou 646000, China. 4. Transplantation Center, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, China. 5. Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, China. Electronic address: greatsailor@163.com.
Abstract
AIMS: Sedum sarmentosum Bunge, a traditional Chinese herbal medicine, has a wide range of clinical effects, including anti-oxidation, anti-inflammation, and anti-cancer properties. In this study, we determined whether S. sarmentosum Bunge Extract (SSBE) has anti-fibrotic effects on renal tissues. MAIN METHODS: We investigated the effects of SSBE on aristolochic acid (AA)-induced injury to renal tubular epithelial cells (RTECs) in vitro and unilateral ureteral obstruction (UUO)-induced renal fibrosis in vivo by evaluating epithelial-to-mesenchymal transition (EMT) and the accumulation of extracellular matrix (ECM) components. Furthermore, we examined the expression levels of TGF-β1 and its receptor. KEY FINDINGS: In cultured RTECs (NRK-52E), AA promoted renal EMT and ECM accumulation by up-regulating the expression of mesenchymal markers and ECM components and by down-regulating the expression of epithelial markers. In addition, AA induced an imbalance between MMP-2 and TIMP-2 and enhanced expression of TGF-β1 and its receptor. SSBE treatment significantly inhibited AA-induced TGF-β1 expression and prevented the induction of EMT and deposition of ECM. In the UUO rats, tubular injury and interstitial fibrosis were obviously increased. SSBE administration protected renal function, as indicated by reduced serum creatinine levels, and alleviated renal interstitial fibrosis. These anti-fibrotic effects were associated with a reduction in TGF-β1 expression and inhibition of EMT and ECM accumulation. SIGNIFICANCE: These findings suggest that SSBE may have therapeutic potential for fibrotic kidney diseases.
AIMS: Sedum sarmentosum Bunge, a traditional Chinese herbal medicine, has a wide range of clinical effects, including anti-oxidation, anti-inflammation, and anti-cancer properties. In this study, we determined whether S. sarmentosum Bunge Extract (SSBE) has anti-fibrotic effects on renal tissues. MAIN METHODS: We investigated the effects of SSBE on aristolochic acid (AA)-induced injury to renal tubular epithelial cells (RTECs) in vitro and unilateral ureteral obstruction (UUO)-induced renal fibrosis in vivo by evaluating epithelial-to-mesenchymal transition (EMT) and the accumulation of extracellular matrix (ECM) components. Furthermore, we examined the expression levels of TGF-β1 and its receptor. KEY FINDINGS: In cultured RTECs (NRK-52E), AA promoted renal EMT and ECM accumulation by up-regulating the expression of mesenchymal markers and ECM components and by down-regulating the expression of epithelial markers. In addition, AA induced an imbalance between MMP-2 and TIMP-2 and enhanced expression of TGF-β1 and its receptor. SSBE treatment significantly inhibited AA-induced TGF-β1 expression and prevented the induction of EMT and deposition of ECM. In the UUO rats, tubular injury and interstitial fibrosis were obviously increased. SSBE administration protected renal function, as indicated by reduced serum creatinine levels, and alleviated renal interstitial fibrosis. These anti-fibrotic effects were associated with a reduction in TGF-β1 expression and inhibition of EMT and ECM accumulation. SIGNIFICANCE: These findings suggest that SSBE may have therapeutic potential for fibrotic kidney diseases.