Construction of a fusion protein between N-terminal 153 peptide of thrombopoietin and erythropoietin

作     者：卢柏松 柳晓兰 黄培堂 

作者机构：1. Institute of Biotechnology 100071 Beijing China 2. Institute of Radiation Medicine 100850 Beijing China 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：1998年第41卷第4期

页      面：426-434页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 

主　　题：thrombopoietin erythropoietin fusion protein. 

摘      要：Thrombopoietin (TPO) functions as a regulator of megakaryocytes in their differentiation and maturation, and is a candidate pharmaceutical for the curing of thrombocytopenia. Erythropoietin (EPO) is a hematopoietic cytokine that regulates the level of red blood cell. It is widely used in renal anemia and tumor associated anemia, and is proved to be safe and effective. In order to study the possibility of using TPO EPO fusion protein for the curing of anemia and thrombocytopenia induced by high dose chemotherapy, a fusion gene is constructed by linking TPO N terminal 153 peptide and EPO mature peptide coding region. The fusion gene is expressed in mammalian cells, revealing that the expression product can support the growth of TPO responsive Ba/F3 mpl cells and EPO dependent Bet 2 cells in the absence of any other stimulating cytokine. It also stimulates the formation of erythroid colonies and megakaryocytic colonies in semi solid bone marrow cultures. These results indicate that the fusion protein has both the in vitro activities of TPO and EPO. The preliminary in vivo experiment reveals that the TPO EPO fusion protein containing cell supernatant raises the platelet level by 37% in mice, while its function on erythroid hematopoiesis remains to be determined. These results indicate that the construction of TPO EPO fusion protein and the further study of its use in high dose chemotherapy are possible