Oleic acid-induced pancreatitis alters expression of transforming growth factor-beta1 and extracellular matrix components in rats.
OBJECTIVE
Extracellular matrix (ECM) components participate in the process of tissue repair and development of fibrosis in the pancreas. We studied the production kinetics of ECM components and transforming growth factor (TGF)-beta1 and identified their production sites in the pancreas following pancreatitis.


METHODS
Pancreatitis was induced in rats by a single intraductal infusion of oleic acid. Gene expression of TGF-betas and ECM components was studied by northern blotting. Pancreatic stellate cell activation was assessed by immunostaining for alpha-smooth muscle actin (alphaSMA) and desmin.


RESULTS
Gene expression of TGF-betas and ECM components was increased in association with pancreatic fibrosis after 1-2 weeks and remained higher than the control levels for the ensuing 12 weeks. Both alphaSMA and desmin were strongly immunostained around small vessels and faintly stained in mesenchymal cells and tubular complexes at 1 week. The combination of staining for alphaSMA plus in situ hybridization for procollagen type III mRNA revealed that procollagen type III mRNA was expressed in both alphaSMA-positive and alphaSMA-negative cells in the mesenchyma.


CONCLUSIONS
Our findings demonstrate that expression of genes for both TGF-betas and ECM components was increased and that both alphaSMA-positive myofibroblasts and mesenchymal cells are the major sources of ECM components after pancreatitis.
Tashiro
Mitsuo
M
Third Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Nakamura
Hayato
H
Taguchi
Masashi
M
Yamaguchi
Taizo
T
Yoshikawa
Hiroyuki
H
Fukumitsu
Ken-ichiro
K
Kihara
Yasuyuki
Y
Otsuki
Makoto
M
D000199:Actins / Q000032:analysis; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D003893:Desmin / Q000032:analysis; D005109:Extracellular Matrix / Q000235:genetics* / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D009130:Muscle, Smooth / Q000737:chemistry; D019301:Oleic Acid / Q000008:administration & dosage; D010179:Pancreas / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D000199:Actins; D024042:Collagen Type I; D024061:Collagen Type III; D003893:Desmin; D005353:Fibronectins; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019301:Oleic Acid