Mayoral Rafael, Fernández-Martínez Amalia, Roy Rosa, Boscá Lisardo, Martín-Sanz Paloma
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain.
Hepatology. 2007 Sep;46(3):813-22. doi: 10.1002/hep.21746.
Caveolae participate in several cellular processes such as vesicular transport, cholesterol homeostasis, regulation of signal transduction, integrin signaling, and cell growth. The expression and functional role of caveolin (Cav), the most abundant protein of caveolae, has been reported in liver and in different hepatocyte cell lines, in human cirrhotic liver, and in hepatocellular carcinomas. The role of Cav-1 in liver regeneration after partial hepatectomy (PH) has been investigated as a model of liver proliferation in vivo. Our results show that Cav-1 increases in liver after PH with a redistribution of the protein from the caveola-enriched domain to the noncaveolar fraction. Moreover, the Cav-1 located in the noncaveolar fraction is phosphorylated in tyrosine 14, even though the Cav-1 gene is dispensable for liver regeneration after PH, as deduced from data obtained with commercially available animals lacking this gene. In addition to this, the proinflammatory stimulation of hepatocytes induces Cav-1 translocation to a noncaveolar fraction and tyrosine 14 phosphorylation mainly through the activation of tyrosine kinases such as Src.
These results support a dynamic role for Cav-1 in liver proliferation both in vivo after PH and in vitro in cultured hepatic cell lines, but with minimal implications for the liver regeneration process.
小窝参与多种细胞过程,如囊泡运输、胆固醇稳态、信号转导调节、整合素信号传导和细胞生长。小窝中最丰富的蛋白质小窝蛋白(Cav)在肝脏、不同的肝细胞系、人类肝硬化肝脏和肝细胞癌中的表达及功能作用已有报道。作为体内肝脏增殖的模型,人们研究了Cav - 1在部分肝切除术后(PH)肝脏再生中的作用。我们的结果表明,PH后肝脏中Cav - 1增加,且该蛋白从小窝富集结构域重新分布到非小窝部分。此外,位于非小窝部分的Cav - 1在酪氨酸14位点被磷酸化,尽管从缺乏该基因的市售动物获得的数据推断,Cav - 1基因对PH后肝脏再生并非必需。除此之外,肝细胞的促炎刺激主要通过激活酪氨酸激酶如Src诱导Cav - 1易位至非小窝部分并使酪氨酸14磷酸化。
这些结果支持Cav - 1在PH后体内和体外培养的肝细胞系中的肝脏增殖中发挥动态作用,但对肝脏再生过程影响极小。