Identification of irisin as a therapeutic agent that inhibits oxidative stress and fibrosis in a murine model of chronic pancreatitis

Biomedicine & Pharmacotherapy

Rongqian Wu¹  Mengzhou Wang¹  Minglong Qiu¹  Tao Wang²  Zheng Wu²  Jia Zhang²  Yifan Ren³  Jianbin Bi³  Yi Lv³ 

[1] Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China;Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China;;National Local Joint Engineering Research Center for Precision Surgery &

关键词: Chronic pancreatitis;    Stellate cell;    Irisin;    Fibrosis;    Oxidative stress;    ER stress;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

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