Relationship between expression of cyclin D1 and impaired liver regeneration observed in fibrotic or cirrhotic rats.
OBJECTIVE
The mechanisms responsible for impaired regenerative ability after hepatic resection observed in chronic liver disease are not fully understood. We have examined the relationships between an altered expression of cell cycle-related proteins in regenerating liver after partial hepatectomy and the impaired regenerative process observed in fibrotic and cirrhotic rats.


METHODS
We performed 70% partial hepatectomy in both control and porcine serum-induced fibrotic rats, and 45% partial hepatectomy in thioacetamide-induced cirrhotic rats because of the high mortality associated with 70% partial hepatectomy. Liver regeneration was monitored by proliferating cell nuclear antigen labeling index and the expression of G1 regulatory cell cycle-related proteins was determined by immunoblot analysis.


RESULTS
Compared with controls, hepatocyte DNA synthesis, and induction of cyclin D1 and p21(CIP1) proteins were delayed but not suppressed in porcine serum-induced fibrotic rats and markedly inhibited in thioacetamide-induced cirrhotic rats. p27(KIP1) protein levels were unaffected by partial hepatectomy and did not differ among all three groups.


CONCLUSIONS
Two distinct rat models of liver fibrosis and cirrhosis showed markedly different proliferative responses after partial hepatectomy. The delay or failure of cyclin D1 induction, but not the increase of p21(CIP1) or p27(KIP1) might be responsible for their impaired liver regeneration.
Kato
Akira
A
First Department of Internal Medicine, Saitama Medical Center, Saitama 350-8550, Japan.
Bamba
Hiromi
H
Shinohara
Masahiko
M
Yamauchi
Atsushi
A
Ota
Shinichi
S
Kawamoto
Chiaki
C
Yoshida
Yukio
Y
D000818:Animals; D019938:Cyclin D1 / Q000096:biosynthesis / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004195:Disease Models, Animal; D006498:Hepatectomy; D008099:Liver / Q000378:metabolism / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D008115:Liver Regeneration; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D044967:Serum; D013853:Thioacetamide
D050759:Cyclin-Dependent Kinase Inhibitor p21; D018809:Proliferating Cell Nuclear Antigen; D013853:Thioacetamide; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004247:DNA; D051358:Cyclin-Dependent Kinase 4