Regulation of hepatic stellate cells by intracellular calcium

描述（由申请人提供）：肝硬化是美国第12大死亡原因，但缺乏有效的治疗方法来预防或治疗肝硬化。肝硬化的主要表现是肝脏的晚期纤维化或瘢痕形成。肝星状细胞是肝纤维化的重要介质，但许多方面的肝星状细胞生物学知之甚少。一个很好的特征是肝星状细胞的肌成纤维分化，通常被称为激活，在患病的肝脏。本研究旨在探索细胞内钙及其效应分子调控肝星状肌成纤维细胞的新途径。第一个目的，我们将研究钙效应分子钙调蛋白激酶II在肝星状细胞功能中的作用。在第二个目标中，我们将确定有利于瘢痕形成的储存成分从肌成纤维肝星状细胞释放的机制。在第三个也是最后一个目标中，我们将测试酶CD73/5'-外核苷酸酶在调节肝星状细胞功能中的作用。该项目的长期目标是确定预防和/或治疗慢性肝病患者肝硬化的新途径。

DESCRIPTION (provided by applicant): Cirrhosis is the 12th leading cause of death in the United States, yet effective treatments to prevent or treat cirrhosis are lacking. The primary manifestation of cirrhosis is advanced fibrosis, or scar formation, in the liver. Hepatic stellate cells are important mediators of liver fibrosis, yet many aspects of hepatic stellate cell biology are poorly understood. One thing that is well characterized is the myofibroblastic differentiation of hepatic stellate cells, often termed activation, in the diseased liver. The purpose of the experiments proposed in this grant application is to identify novel pathways by which intracellular calcium and its effector molecules regulate myofibroblastic hepatic stellate cells. I the first aim, we will investigate the role of the calcium effector molecule calmodulin kinase II i hepatic stellate cell function. In the second aim, we will identify mechanisms by which stored components favoring scar formation are released from myofibroblastic hepatic stellate cells. In the third and final aim, we will test the role of the enzyme CD73/5'-ectonucleotidase in the regulation of hepatic stellate cell function. The long-term goals of this project are to identify novel pathways for the prevention and/or treatment of cirrhosis in patients with chronic liver disease.