Effect of recombinant human growth hormone and interferon gamma on hepatic collagen synthesis and proliferation of hepatic stellate cells in cirrhotic rats.
BACKGROUND
Fibrosis plays a key role in the development of liver cirrhosis. In this study, we investigated the effect of growth hormone and interferon gamma on hepatic collagen synthesis and the proliferation of hepatic stellate cells in a cirrhotic rat model.


METHODS
Cirrhosis was induced in rats using carbon tetrachloride. Rats were simultaneously treated with daily subcutaneous injections of recombinant human growth hormone or interferon gamma combined with recombinant human growth hormone. The control group was given saline. The relative content of type I and type IV collagen was assessed by indirect immunofluorescence analysis. Activated hepatic stellate cells were prepared from cirrhotic rats. The 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) method was used to assess the effects of recombinant human growth hormone and interferon gamma on these cells in vitro.


RESULTS
Both qualitative and quantitative analysis showed that type I and type IV collagen secretion increased with time after recombinant human growth hormone administration and was significantly higher than control and recombinant human growth hormone combined with interferon gamma administration. In vitro, recombinant human growth hormone significantly stimulated hepatic stellate cell proliferation in a concentration-dependent manner (10(-3)-10(-1) mg/100 μL), and interferon gamma (10(-2)-10(-1) μg/100 μL) significantly inhibited their growth compared to the control group. Interferon gamma combined with recombinant human growth hormone eliminated this growth-promoting effect to a certain degree in a concentration-dependent manner (10(-1) μg/100 μL, P<0.05, 10(-2)-10(-3) μg/100 μL, P>0.05) and a time-dependent manner (P<0.05).


CONCLUSIONS
Recombinant human growth hormone increased collagen secretion in cirrhotic rats in vivo and promoted the proliferation of hepatic stellate cells from cirrhotic rats in vitro. It is possible that concurrent interferon gamma therapy can offset these side-effects of recombinant human growth hormone.
Department of Hepatobiliopancreatic Surgery, Sichuan University, Chengdu, China.
Yong-Hua
YH
Chen
Bing-Qing
BQ
Du
Zhen-Jiang
ZJ
Zheng
Guang-Ming
GM
Xiang
Xu-Bao
XB
Liu
Gang
G
Mai
D000818:Animals; D002251:Carbon Tetrachloride; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis*; D024141:Collagen Type IV / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D010634:Phenobarbital; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D024042:Collagen Type I; D024141:Collagen Type IV; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007371:Interferon-gamma; D002251:Carbon Tetrachloride; D010634:Phenobarbital