In situ expression of fibrogenic growth factors and their receptors in biliary atresia: comparison between early and late stages.
Progressive fibrosis, despite successful surgical treatment, is one of the serious complications of biliary atresia. To understand the mechanism of this fibrosis, the in situ expression of fibrogenic growth factors (TGF-beta and PDGF) and their corresponding receptors was studied by immunohistochemistry using frozen sections. The results were compared between the early (n=12) and late (n=6) stages. The early stage was characterized by abundant expression of all ligands and receptors, together with type I procollagen (PC-I). The major cellular sources were activated fibroblasts/myofibroblasts distributed mostly in the portal tracts. Macrophages also expressed all the ligands and the receptors, but to a lesser degree. Bile duct cells strongly expressed TGF-beta RI and RII and PDGF AA and BB, but focally expressed TGF-beta. All of these decreased in the late stage of biliary atresia. These results suggest that TGF-beta and PDGF play important roles in the fibrogenesis of biliary atresia, especially in its early stage, acting either by autocrine or paracrine mechanisms involving activated fibroblasts/myofibroblasts, bile duct cells, and macrophages.
Faiz Kabir Uddin Ahmed
A
A
Department of Pediatric Surgery, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Ohtani
H
H
Nio
M
M
Funaki
N
N
Iwami
D
D
Kumagai
S
S
Sato
E
E
Nagura
H
H
Ohi
R
R
D000328:Adult; D000368:Aged; D001656:Biliary Atresia / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011347:Procollagen / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D010982:Platelet-Derived Growth Factor; D011347:Procollagen; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor