Changes in activin and activin receptor subunit expression in rat liver during the development of CCl4-induced cirrhosis.
Amounts of betaA-activin, betaC-activin, activin receptor subunits ActRIIA and ActRIIB mRNA, and betaA- and betaC-activin subunit protein immunoreactivity were investigated in male Lewis rats, either untreated or after 5 or 10 weeks of CCl(4) treatment to induce cirrhosis. Apoptosis was assessed histologically and with an in situ cell death detection kit (TUNEL). Reverse transcription and polymerase chain reaction were used to evaluate mRNA levels. Activin betaA- and betaC-subunit immunoreactivity was studied by immunohistochemistry using specific monoclonal antibodies. Hepatocellular apoptosis (P<0.001), increased betaA- and betaC-activin mRNAs (three- to fourfold; P<0.01) and increased betaA- and betaC-activin tissue immunoreactivity were evident, whereas ActRIIA mRNA concentrations fell (30%; P<0.01) after 5 weeks of CCl(4) treatment. The mRNA concentrations at 10 weeks were not significantly different from controls, despite extensive hepatic nodule formation. We conclude that the increased activin subunit expression is associated with apoptosis, rather than hepatic fibrosis and nodule formation.
Gold
Elspeth J
EJ
Department of Anatomy and Structural Biology and Centre for Gene Research, University of Otago, Otago School of Medical Sciences, P.O. Box 913, Dunedin, New Zealand.
Francis
Richard J B
RJ
Zimmermann
Arthur
A
Mellor
Sally L
SL
Cranfield
Mark
M
Risbridger
Gail P
GP
Groome
Nigel P
NP
Wheatley
Antony M
AM
Fleming
Jean S
JS
D030301:Activin Receptors, Type II / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002251:Carbon Tetrachloride / Q000633:toxicity; D018450:Disease Progression; D015870:Gene Expression; D020287:In Situ Nick-End Labeling; D028322:Inhibin-beta Subunits / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction
C504188:Inhbc protein, rat; D012333:RNA, Messenger; C103008:inhibin beta A subunit; D028322:Inhibin-beta Subunits; D002251:Carbon Tetrachloride; D030301:Activin Receptors, Type II; C425585:activin receptor type II-A; C425584:activin receptor type II-B