Liver: Growth hormone in liver fibrosis.
Liver: Growth hormone in liver fibrosis.
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DOI：
10.1038/nrgastro.2014.165
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发表时间：
2014-10-01
期刊：
影响因子：
--
通讯作者：
Greenhill, Claire
中科院分区：
文献类型：
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作者：
Greenhill, Claire
最近发表在《肝病学》上的一项研究报告说，对生长激素的抵抗增加了炎症性胆汁淤积小鼠模型的肝纤维化。已知生长激素抵抗与肝纤维化有关;然而，抵抗是否仅仅是由于肝硬化引起的肝细胞功能障碍的结果，或者是否在疾病发展中起因果作用一直存在争议。为了确定这种关系的性质，Emilio Casanova和同事将缺乏生长激素受体（Ghr-/-）编码基因的小鼠与炎症性胆汁淤积和肝纤维化（Mdr 2-/-）小鼠模型进行杂交。产生的双敲除小鼠血清中与肝损伤和胆汁淤积相关的标志物水平升高，与Mdr 2-/-小鼠相比，肝脏中广泛的胆管增殖和增加的胶原沉积。这一发现表明生长激素抵抗增加了肝纤维化表型的严重程度。此外，喂食含1%胆酸的饮食的Ghr-/-小鼠的肝损伤、胆道梗死和活性氧水平增加，以及肝细胞凋亡增加。在体外实验中，与野生型肝细胞相比，从用脱氧胆酸、转化生长因子β或TNF（单独或联合）处理的Ghr-/-小鼠中分离的肝细胞的细胞活力降低。总之，这些结果表明，与野生型小鼠相比，Ghr的缺失使小鼠更容易受到胆汁酸和细胞因子的肝损伤。
Resistance to growth hormone increases liver fibrosis in a mouse model of inflammatory cholestasis, reports a study recently published in Hepatology. Growth hormone resistance is known to be associated with liver fibrosis; however, whether the resistance is simply the result of hepatocyte malfunction owing to cirrhosis or if it has a causal role in disease development has been debated. To determine the nature of this relationship, Emilio Casanova and colleagues crossed mice lacking the gene that encodes the growth hormone receptor (Ghr–/–) with a mouse model of inflammatory cholestasis and liver fibrosis (Mdr2–/–).The resulting double knockout mice had raised serum levels of markers associated with liver damage and cholestasis, extensive bile duct proliferation and increased collagen deposition in the liver compared with Mdr2–/–mice. This finding suggests that growth hormone resistance increases the severity of the liver fibrosis phenotype. Furthermore, Ghr–/–mice that were fed a diet containing 1% cholic acid had increased levels of liver damage, biliary infarcts and reactive oxygen species, as well as increased hepatocyte apoptosis. In an in vitro experiment, hepatocytes isolated from Ghr–/–mice that were treated with deoxycholic acid, transforming growth factor β or TNF (either alone or in combination) had reduced cell viability compared with wild-type hepatocytes. Together, these results indicate that loss of Ghr leaves mice more susceptible to liver injury from bile acids and cytokines compared with wild-type mice.