Localisation and semiquantitative assessment of hepatic procollagen mRNA in primary biliary cirrhosis.
BACKGROUND
Chronic liver disease is characterised by excessive deposition of collagen and other extracellular matrix proteins, produced mainly, but not exclusively, by activated hepatic stellate cells in the perisinusoidal space. In primary biliary cirrhosis (PBC) fibrosis is concentrated mainly around the portal tracts.


OBJECTIVE
To examine the hypothesis that, in addition to hepatic stellate cells, portal tract fibroblasts might play a significant role in the deposition of collagen in PBC.


METHODS
Fifty liver biopsy specimens from patients with PBC were studied. An in situ hybridisation technique was adapted to localise and measure semiquantitatively type I procollagen mRNA in formalin fixed, paraffin wax embedded sections, using an 35S labelled cRNA probe specific for the alpha 1 chain of rat type I procollagen. Hepatic fibrogenic activity was also assessed using serum type III procollagen peptide (PIIINP).


RESULTS
In PBC, type I procollagen gene expression was significantly increased. Signal was localised mainly in and around inflamed portal tracts, to cells which had the appearances of portal fibroblasts. Signal activity in these cells correlated with the degree of portal fibrosis and inflammation and also with serum PIIINP concentrations.


CONCLUSIONS
Results are consistent with the hypothesis that the excessive extracellular matrix, deposited within the liver in PBC, is synthesised not only by hepatic stellate cells but also by portal tract fibroblasts. The semiquantitative assessment of procollagen mRNA in liver biopsy specimens may provide a useful method of evaluating the rate of synthesis of collagen and therefore disease activity in patients with PBC.
Goddard
C J
CJ
Liver Unit, Manchester Royal Infirmary, UK.
Smith
A
A
Hoyland
J A
JA
Baird
P
P
McMahon
R F
RF
Freemont
A J
AJ
Shomaf
M
M
Haboubi
N Y
NY
Warnes
T W
TW
D015415:Biomarkers / Q000097:blood; D005347:Fibroblasts / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D008099:Liver / Q000737:chemistry* / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000097:blood / Q000235:genetics*; D011168:Portal System; D011347:Procollagen / Q000097:blood / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*
D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; D012333:RNA, Messenger; C041876:procollagen Type III-N-terminal peptide; C042813:procollagen type I carboxy terminal peptide