Growth factor and procollagen type I gene expression in human liver disease.
OBJECTIVE
Growth factors have been implicated in the pathogenesis of liver fibrosis, a major determinant of the clinical course of chronic liver disease. The aim of this study was to study the relationship of growth factor expression to inflammation and fibrosis in a variety of human liver diseases.


METHODS
We studied by in situ hybridization the expression of transforming growth factor (TGF) beta 1, platelet-derived growth factor (PDGF) A and PDGF-B, and procollagen type I (pro-I) messenger RNAs (mRNAs) in liver diseases of various etiologies.


RESULTS
Pro-I mRNA was expressed by mesenchymal cells at sites of inflammation and scarring, where TGF-beta 1 immunoreactivity was often found, and by perisinusoidal cells. TGF-beta 1 and PDGF-A mRNAs were expressed mainly by mononuclear cells and proliferating ductular cells. TGF-beta 1 mRNA was also expressed by perisinusoidal cells. PDGF-A gene expression was more common than that of PDGF-B. Pro-I and TGF-beta 1 expression correlated with both ductular proliferation and tissue inflammation, whereas PDGF-A and PDGF-B only correlated with ductular proliferation.


CONCLUSIONS
Our data suggest that TGF-beta 1 and PDGF are involved in human liver inflammation and fibrosis. The expression of growth factor mRNAs in proliferating ductular cells may indicate a role for these cells in liver fibrogenesis and may help explain the pathophysiology of conditions such as biliary atresia progressing to fibrosis despite the absence of marked inflammation.
Malizia
G
G
Divisione di Medicina, Ospedale V. Cervello, Palermo, Italy.
Brunt
E M
EM
Peters
M G
MG
Rizzo
A
A
Broekelmann
T J
TJ
McDonald
J A
JA
D015870:Gene Expression; D006133:Growth Substances / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008099:Liver / Q000378:metabolism; D008107:Liver Diseases / Q000235:genetics* / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D011347:Procollagen / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D016212:Transforming Growth Factor beta / Q000235:genetics
D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D011347:Procollagen; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C075278:platelet-derived growth factor A