Pressure activates rat pancreatic stellate cells.
S Watanabe, Y Nagashio, H Asaumi, Y Nomiyama… - Pancreas, 2004 - journals.lww.com
S Watanabe, Y Nagashio, H Asaumi, Y Nomiyama, M Taguchi, M Tashiro, Y Kihara…
Pancreas, 2004•journals.lww.comBackground/Aim: Pancreatic stellate cells (PSCs) play a central role in the development of
pancreatic fibrosis. In chronic pancreatitis, pancreatic tissue pressure is higher than that of
normal pancreas. We hypothesized that PSCs could be a potential target for tissue pressure
in chronic pancreatitis and increased pancreatic tissue pressure promoted pancreatic
fibrosis. Therefore, we examined the effects of pressure on rat PSC activation. Methods:
PSCs were isolated as described previously. Pressure was applied to PSCs by instilling …
pancreatic fibrosis. In chronic pancreatitis, pancreatic tissue pressure is higher than that of
normal pancreas. We hypothesized that PSCs could be a potential target for tissue pressure
in chronic pancreatitis and increased pancreatic tissue pressure promoted pancreatic
fibrosis. Therefore, we examined the effects of pressure on rat PSC activation. Methods:
PSCs were isolated as described previously. Pressure was applied to PSCs by instilling …
Background/Aim: Pancreatic stellate cells (PSCs) play a central role in the development of pancreatic fibrosis. In chronic pancreatitis, pancreatic tissue pressure is higher than that of normal pancreas. We hypothesized that PSCs could be a potential target for tissue pressure in chronic pancreatitis and increased pancreatic tissue pressure promoted pancreatic fibrosis. Therefore, we examined the effects of pressure on rat PSC activation.
Methods: PSCs were isolated as described previously. Pressure was applied to PSCs by instilling compressed helium gas into sealed plates. p38 mitogen-activated protein kinase (MAPK) and alpha-smooth muscle actin (alpha-SMA) protein levels in PSCs were measured by Western blot analysis. Transforming growth factor-ß1 (TGF-ß1) concentration in medium was investigated by ELISA. Collagen type I mRNA expression and collagen secretion were assessed by quantitative polymerase chain reaction and Sirius red dye binding assay, respectively.
Results: Alpha-SMA expression was significantly increased by application of pressure on PSCs. Pressure rapidly increased the phosphorylation of p38 MAPK, and pretreatment of PSCs with p38 MAPK inhibitor (SB203580) suppressed pressure-induced alpha-SMA expression. Pressure significantly promoted activated TGF-ß1 secretion, collagen type I mRNA expression and collagen secretion.
Conclusions: These results indicate that increased pancreatic tissue pressure activates PSCs through p38 MAPK pathway and, promotes pancreatic fibrosis.
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