Yifan Ren1, Jia Zhang1, Mengzhou Wang1, Jianbin Bi1, Tao Wang1, Minglong Qiu2, Yi Lv1, Zheng Wu3, Rongqian Wu4. 1. National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China; Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China. 2. Department of Orthopedic, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. 3. Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China. Electronic address: woozheng@mail.xjtu.edu.cn. 4. National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China. Electronic address: rwu001@mail.xjtu.edu.cn.
Abstract
BACKGROUND: Abnormal activation of pancreatic stellate cells (PSCs) plays a crucial role in the pathogenesis of chronic pancreatitis (CP). Irisin, an exercise-induced hormone, has been shown to mitigate liver fibrosis by inhibiting the activation of hepatic stellate cells. However, the effect of irisin in CP has not been evaluated. METHODS: This study aimed to determine whether irisin is protective in CP. CP was induced by 6 IP injections of cerulein (50 μg/kg/body weight). HPSCs were treated with 5 ng/ml TGF-β1 as in vitro experiment. RESULTS: Our results showed that repeated cerulein injection induced severe pancreatic injury and fibrosis in mice and the serum irisin level in cerulein-treated mice decreased as in CP patients. Excessive oxidative and ER stress was also present in the pancreas of cerulein-treated mice. Irisin treatment significantly alleviated pancreatic injury and fibrosis, which was associated with reduced oxidative and ER stress. In cultured PSCs, irisin directly inhibited TGF-β-induced α-SMA and collagen I expression. This effect appears to be mediated through downregulation of kindlin-2 and inhibition of the SMAD2/3 pathway. CONCLUSIONS: Irisin alleviated pancreatic injury and fibrosis, which was associated with reduced oxidative and ER stress. Thus, irisin may offer therapeutic potential for patients with CP.
BACKGROUND: Abnormal activation of pancreatic stellate cells (PSCs) plays a crucial role in the pathogenesis of chronic pancreatitis (CP). Irisin, an exercise-induced hormone, has been shown to mitigate liver fibrosis by inhibiting the activation of hepatic stellate cells. However, the effect of irisin in CP has not been evaluated. METHODS: This study aimed to determine whether irisin is protective in CP. CP was induced by 6 IP injections of cerulein (50 μg/kg/body weight). HPSCs were treated with 5 ng/ml TGF-β1 as in vitro experiment. RESULTS: Our results showed that repeated cerulein injection induced severe pancreatic injury and fibrosis in mice and the serum irisin level in cerulein-treated mice decreased as in CP patients. Excessive oxidative and ER stress was also present in the pancreas of cerulein-treated mice. Irisin treatment significantly alleviated pancreatic injury and fibrosis, which was associated with reduced oxidative and ER stress. In cultured PSCs, irisin directly inhibited TGF-β-induced α-SMA and collagen I expression. This effect appears to be mediated through downregulation of kindlin-2 and inhibition of the SMAD2/3 pathway. CONCLUSIONS:Irisin alleviated pancreatic injury and fibrosis, which was associated with reduced oxidative and ER stress. Thus, irisin may offer therapeutic potential for patients with CP.