Li Wang1, Ai-Li Cao1, Yang-Feng Chi2, Zheng-Cai Ju3, Pei-Hao Yin2, Xue-Mei Zhang4, Wen Peng5. 1. Laboratory of Renal Disease, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China. 2. Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China. 3. Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. 4. Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address: xuemzhang@fudan.edu.cn. 5. Laboratory of Renal Disease, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China; Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China. Electronic address: pengwen_01@vip.sina.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: You-gui Pill (YGP), a traditional Chinese medicinal prescription, was widely used to warm and recuperate "kidney-yang" clinically for hundreds of years in China. Recent studies found that YGP had a potential benefit for renoprotection. AIM OF THE STUDY: The present study aimed to elucidate the in vivo and in vitro efficacy of YGP on renal tubulointerstitial fibrosis, and the molecular mechanism is also investigated. MATERIALS AND METHODS: Rat renal tubulointerstitial fibrosis model was elicited by unilateral ureteral obstruction (UUO). Sprague-Dawley rats underwent UUO and were studied after 14 days. Animals were randomly subjected to six groups: sham, UUO, UUO/YGP (0.14, 0.42, 1.26g/kg/d), and UUO/enalapril (10mg/kg/d). HE, Masson and ELISA were used for evaluate renal injury and function. Immunohistochemical analysis and western blot were used to detect the expressions of α-SMA, fibronectin, collagen matrix and Smads. In vitro studies were investigated in TGF-β1-stiumlated NRK-49F cell line. RESULTS: Oral administration of YGP significantly decreased UUO-induced inflammatory cell infiltration, tubular atrophy and interstitial fibrosis, and there was no significant difference between YGP at 1.26g/kg and enalapril at 10mg/kg treatment (P>0.05). Meanwhile, serum creatinine and blood urea nitrogen levels were reduced dramatically (P<0.01). In coincide with the decreased of TGF-β1, α-SMA, fibronectin and collagen matrix expressions were also declined with YGP treatment in both UUO kidneys and TGF-β1-stimulated NRK-49F cell line. Additionally, nuclear translocation of p-Smad2/3 was markedly down-regulated by YGP (P<0.001), with a relative mild up-regulated expression of Smad7 (P<0.05). CONCLUSIONS: Our findings demonstrate that YGP had a renoprotective effect in ameliorating renal tubulointerstitial fibrosis, and this activity possibly via suppression of the TGF-β and its downstream regulatory signaling pathway, including Smad2/3.
ETHNOPHARMACOLOGICAL RELEVANCE: You-gui Pill (YGP), a traditional Chinese medicinal prescription, was widely used to warm and recuperate "kidney-yang" clinically for hundreds of years in China. Recent studies found that YGP had a potential benefit for renoprotection. AIM OF THE STUDY: The present study aimed to elucidate the in vivo and in vitro efficacy of YGP on renal tubulointerstitial fibrosis, and the molecular mechanism is also investigated. MATERIALS AND METHODS:Ratrenal tubulointerstitial fibrosis model was elicited by unilateral ureteral obstruction (UUO). Sprague-Dawley rats underwent UUO and were studied after 14 days. Animals were randomly subjected to six groups: sham, UUO, UUO/YGP (0.14, 0.42, 1.26g/kg/d), and UUO/enalapril (10mg/kg/d). HE, Masson and ELISA were used for evaluate renal injury and function. Immunohistochemical analysis and western blot were used to detect the expressions of α-SMA, fibronectin, collagen matrix and Smads. In vitro studies were investigated in TGF-β1-stiumlated NRK-49F cell line. RESULTS: Oral administration of YGP significantly decreased UUO-induced inflammatory cell infiltration, tubular atrophy and interstitial fibrosis, and there was no significant difference between YGP at 1.26g/kg and enalapril at 10mg/kg treatment (P>0.05). Meanwhile, serum creatinine and blood ureanitrogen levels were reduced dramatically (P<0.01). In coincide with the decreased of TGF-β1, α-SMA, fibronectin and collagen matrix expressions were also declined with YGP treatment in both UUO kidneys and TGF-β1-stimulated NRK-49F cell line. Additionally, nuclear translocation of p-Smad2/3 was markedly down-regulated by YGP (P<0.001), with a relative mild up-regulated expression of Smad7 (P<0.05). CONCLUSIONS: Our findings demonstrate that YGP had a renoprotective effect in ameliorating renal tubulointerstitial fibrosis, and this activity possibly via suppression of the TGF-β and its downstream regulatory signaling pathway, including Smad2/3.
Authors: Elisabeth Schinner; Veronika Wetzl; Andrea Schramm; Frieder Kees; Peter Sandner; Johannes-Peter Stasch; Franz Hofmann; Jens Schlossmann Journal: FEBS Open Bio Date: 2017-03-01 Impact factor: 2.693
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