Type VI collagen gene expression in experimental liver fibrosis: quantitation and spatial distribution of mRNAs, and immunodetection of the protein.
Type VI collagen is a minor but essential matrix component in the liver. In this study, we utilized an acute and a chronic injury model to clarify the process of liver fibrosis in rats by administration of carbon tetrachloride. Collagen gene expression, with particular emphasis on type VI collagen, was studied by molecular hybridization techniques. The alpha 2(VI) collagen mRNA levels were markedly elevated on day 3 of acute injury and were approximately at the same high level at 7 and 14 weeks of chronic injury, as determined by Northern hybridizations and slot-blot analyses. Marked enhancement of type I collagen gene expression was similarly noted at these time points. The activation of collagen gene expression in acute injury, as determined by in situ hybridization, was particularly prominent in the vicinity of the central veins. Indirect immunofluorescence demonstrated marked accumulation of type VI collagen protein as early as day 3 of acute injury, and the reaction appeared to be initiated in the proximity of central veins. These results indicate that type VI collagen gene expression, together with other connective tissue components, including type I collagen, is activated in the early stages of the fibrotic process. Type VI collagen accumulation may contribute to the distorted architecture and functional impairment of the liver in hepatic fibrosis.
Takahara
T
T
Department of Dermatology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, USA.
Sollberg
S
S
Muona
P
P
Uitto
J
J
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D003094:Collagen / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D012333:RNA, Messenger; D003094:Collagen