Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 25, Issue 4, Pages 2213-2227Publisher
WILEY
DOI: 10.1111/jcmm.16213
Keywords
chronic pancreatitis; fibrosis; inflammatory; nuclear factor‐ kappa B; pancreatic stellate cells
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Funding
- Natural Science Research Project of Shaanxi Province [2018JM7085]
- National Natural Science Foundation of China [81673816]
- Subject Innovation Team of Shaanxi University of Chinese Medicine [2019-YL14]
- Key Basic Research Project of Shaanxi Province [2017ZDJC-14]
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The study indicates that TGF-β1 can induce the activation of the NF-κB pathway in PSCs by regulating p-TAK1, and the NF-κB pathway in PSCs may be a target of chronic inflammation and fibrosis.
The activation of pancreatic stellate cells (PSCs) plays a critical role in the progression of pancreatic fibrosis. Nuclear factor-kappa B (NF-kappa B) is associated with chronic pancreatitis (CP). Previous evidence indicated that NF-kappa B in acinar cells played a double-edged role upon pancreatic injury, whereas NF-kappa B in inflammatory cells promoted the progression of CP. However, the effects of NF-kappa B in PSCs have not been studied. In the present study, using two CP models and RNAi strategy of p65 in cultured PSCs, we found that the macrophage infiltration and MCP-1 expression were increased, and the NF-kappa Bp65 protein level was elevated. NF-kappa Bp65 was co-expressed with PSCs. In vitro, TGF-beta 1 induced overexpression of the TGF-beta receptor 1, phosphorylated TGF-beta 1-activated kinase 1 (p-TAK1) and NF-kappa B in the PSCs. Moreover, the concentration of MCP-1 in the supernatant of activated PSCs was elevated. The migration of BMDMs was promoted by the supernatant of activated PSCs. Further knockdown of NF-kappa Bp65 in PSCs resulted in a decline of BMDM migration, accompanied by a lower production of MCP-1. These findings indicate that TGF-beta 1 can induce the activation of NF-kappa B pathway in PSCs by regulating p-TAK1, and the NF-kappa B pathway in PSCs may be a target of chronic inflammation and fibrosis.
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