Overexpression of Smad6 exacerbates pancreatic fibrosis in murine caerulein-induced chronic pancreatic injuries.
OBJECTIVE
We examined the effect of the overexpression of Smad6 on pancreatic fibrosis after chronic pancreatic injury.


METHODS
Chronic pancreatic injury was induced in transgenic mice overexpressing Smad6 (Tg mice) in acini and wild-type (Wt) mice by 3 episodes of acute pancreatitis per week for 1 to 4 consecutive weeks. Acute pancreatitis was elicited by 6 intraperitoneal injections of caerulein (Cn) at 50 microg/kg of body weight at hourly intervals. Pancreatic fibrosis was evaluated by histological examination and hydroxyproline content before and 1, 2, 3, and 4 weeks of repetitive episodes of Cn-induced acute pancreatitis. We further determined transforming growth factor beta1 (TGF-beta1) messenger RNA expression and trypsin activity in the pancreas.


RESULTS
After repetitive episodes of acute pancreatitis, pancreatic fibrosis in Tg mice was significantly severer than that in Wt mice at all time points (weeks 1-4). The expression of TGF-beta1 messenger RNA and the activity of trypsin in the pancreas in the Tg mice were significantly high compared with those in the Wt mice at all corresponding time points after repetitive episodes of acute pancreatitis.


CONCLUSIONS
These results demonstrated that overexpression of Smad6 in acini enhanced the development of pancreatic fibrosis after chronic pancreatic injury.
Miyamoto
Tamao
T
Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
Nakamura
Hayato
H
Nagashio
Yoshikuni
Y
Asaumi
Hiroshi
H
Harada
Masaru
M
Otsuki
Makoto
M
D000818:Animals; D002108:Ceruletide / Q000633:toxicity; D018450:Disease Progression; D005355:Fibrosis; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D050500:Pancreatitis, Chronic / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D051905:Smad6 Protein / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism; D014357:Trypsin / Q000032:analysis / Q000378:metabolism
D051905:Smad6 Protein; C497803:Smad6 protein, mouse; D016212:Transforming Growth Factor beta; D002108:Ceruletide; D014357:Trypsin