期刊
HEPATOLOGY
卷 54, 期 3, 页码 1020-1030出版社
WILEY-BLACKWELL
DOI: 10.1002/hep.24467
关键词
-
资金
- National Natural Science Foundation of China [30770970]
- Science and Technology Commission of Shanghai Municipality [064119520]
- National Science and Technology Major Project [2009ZX09310-006]
The key factors in the pathogenesis of liver fibrosis are the activation and proliferation of hepatic stellate cells (HSCs), which express integrin alpha v beta 3 after activation. This study aimed to explore the potential of (99m)Tc-labeled cyclic arginine-glycine-aspartic acid pentapeptide (cRGD) as a single photon emission computed tomography (SPECT) radiotracer to image hepatic integrin alpha v beta 3 expression to reflect HSC activity in fibrotic livers. Rat models of liver fibrosis caused by thioacetamide or carbon tetrachloride (CCl(4)) treatment were employed to examine the expression and distribution of integrin alpha v beta 3 during fibrotic progression or regression. The binding activity of radiolabeled cRGD to integrin alpha v beta 3 was assessed in liver sections. SPECT was performed to determine hepatic integrin alpha v beta 3 expression in rats with different stages of liver fibrosis. Protein and messenger RNA (mRNA) levels of integrin alpha v and beta 3 subunits were increased with the progression of liver fibrosis and reduced with its regression. The cell type that expressed the majority of integrin alpha v beta 3 in fibrotic livers was found to be activated HSCs. The cRGD binding to activated HSCs displayed a high receptor-coupling affinity and an abundant receptor capacity. Iodine-125 ((125)I)-labeled cRGD bound to fibrotic liver sections and the binding activity was the highest in advanced fibrosis. Intravenously administered carboxyfluorescein-labeled cRGD was accumulated in fibrotic liver, and the accumulation amount was increased with the progression and reduced with the regression of fibrosis. A SPECT imaging study with (99m)Tc-labeled cRGD as a tracer demonstrated that the radioactivity ratio of liver to heart increased progressively along with severity of hepatic fibrosis. Conclusion: Hepatic integrin alpha v beta 3 expression in fibrotic liver reflects HSC activity and its imaging using (99m)Tc-labeled cRGD as a SPECT radiotracer may distinguish different stages of liver fibrosis in rats. (HEPATOLOGY 2011;54:1020-1030)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据