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Role of the spleen in liver fibrosis in rats may be mediated by transforming growth factor β ‐1
Author(s) -
AKAHOSHI TOMOHIKO,
HASHIZUME MAKOTO,
TANOUE KAZUO,
SHIMABUKURO RINSHYUN,
GOTOH NORIKAZU,
TOMIKAWA MORIMASA,
SUGIMACHI KEIZO
Publication year - 2002
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1046/j.1440-1746.2002.02667.x
Subject(s) - medicine , spleen , thioacetamide , splenectomy , fibrosis , hepatocyte , hepatic fibrosis , transforming growth factor , liver regeneration , endocrinology , immunohistochemistry , pathology , regeneration (biology) , biology , in vitro , biochemistry , microbiology and biotechnology
Background: The effect of the spleen on the cirrhotic liver is unknown.
Transforming growth factor‐β1 (TGF‐β1), which plays a crucial role in the matrix production during liver fibrosis, is an inhibitory factor regarding the regeneration of hepatocytes. In this study, we investigated the TGF‐β1 production in the spleen of cirrhotic rats and the effects of a splenectomy on the healing process from liver fibrosis. Methods: Thirty‐six Wister male rats were used. Thioacetamide (TAA) was administered intraperitoneally for 24 weeks. The rats underwent either a sham operation (TAA + Sham) or a splenectomy (TAA + SPL). The improvements in liver fibrosis and liver regeneration were investigated 10, 30 and 60 days after the operations in each group. The effect of a splenectomy on the plasma concentration of TGF‐β1 in the portal vein was investigated by ELISA. The TGF‐β1 expressions in the spleen were measured using immunohistochemical staining and the degree of such expression was measured using RT‐PCR. The activity of TGF‐β1 in the portal vein of TAA + Sham and TAA + SPL was assessed by the inhibiting effect of rat parenchymal hepatocyte proliferation in primary culture. Results: Liver regeneration (PCNA‐labeling index) in the TAA + SPL rats was stimulated more at 10 and 30 days after the operation ( P < 0.05) than in the TAA + Sham rats, and the improvement of liver fibrosis (fibrosis rate) in the TAA + SPL rats was higher at 60 days ( P < 0.05) than in the TAA + Sham rats. The plasma concentration of TGF‐β1 of the portal vein in TAA + SPL rats was significantly lower than in the TAA + Sham rats for each period. Immunohistochemically, TGF‐β1‐positive stained cells were recognized in the spleen macrophages in the red pulp of cirrhotic rats. The plasma of the TAA + Sham rats at 10 and 30 days after the operation was significantly stronger than that of the TAA + SPL rats in inhibiting the proliferation of rat hepatocytes of primary culture. Inhibitory effects were then dose‐dependently neutralized by monoclonal TGF‐β1 antibody. Conclusion: Spleen‐derived TGF‐β1 may thus play an inhibitory role in the healing of liver cirrhosis by inhibiting the regeneration of the damaged liver.