Activated pancreatic stellate cells (PSCs) are the main source of extracellular matrix proteins in pancreatic fibrosis during chronic pancreatitis (CP). This study investigated the role of Hic-5, a TGF-β1-induced protein, in PSC activation and CP development. Hic-5 expression was significantly upregulated in activated PSCs from human CP tissue and a caerulein-induced mouse CP model. Hic-5 deficiency attenuated pancreatic fibrosis and PSC activation in mice. Mechanistically, Hic-5 knockdown inhibited the TGF-β/Smad2 signaling pathway, reducing collagen production and α-SMA expression. The study suggests Hic-5 as a potential marker of activated PSCs and a therapeutic target for CP.
Publisher
Scientific Reports
Published On
Nov 05, 2020
Authors
Lin Gao, Xiao-Feng Lei, Aya Miyauchi, Masahito Noguchi, Tomokatsu Omoto, Shogo Haraguchi, Takuro Miyazaki, Akira Miyazaki, Joo-ri Kim-Kaneyama
Tags
pancreatic stellate cells
chronic pancreatitis
Hic-5
TGF-β1
fibrosis
signaling pathway
therapeutic target
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