Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 126, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2020.110101
Keywords
Chronic pancreatitis; Stellate cell; Irisin; Fibrosis; Oxidative stress; ER stress
Funding
- National Nature Science Foundation of China [81770491]
- Ministry of Education Innovation Team Development Program of China [IRT16R57]
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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 mu g/kg/body weight). HPSCs were treated with 5 ng/ml TGF-beta 1 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-beta-induced alpha-SMA and collagen I expression. This effect appears to be mediated through down-regulation 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.
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