Transgenic expression of leukemia inhibitory factor inhibits both rod and cone gene expression. Gp130 regulates cone gene expression.
Transgenic expression of leukemia inhibitory factor inhibits both rod and cone gene expression. Gp130 regulates cone gene expression.
复制标题
白血病抑制因子的转基因表达抑制视杆细胞和视锥细胞基因的表达。
DOI：
10.1007/0-387-32442-9_22
复制
发表时间：
2006
影响因子：
--
通讯作者：
Graham,DiancaR
中科院分区：
文献类型：
--
作者：
Ash,JohnD;Graham,DiancaR
白血病抑制因子(LIF)是白介素6(IL-6)家族的一员，还包括抑癌素M、睫状神经营养因子(CNTF)、白介素11和心肌营养素-1。根据常见的酪氨酸激酶受体gp130的激活，该家族的成员被组合在一起。(IP et al，1992)包括LIF和CNTF在内的gp130激活配体的表达已定位于视网膜中的Muller胶质细胞和小胶质细胞。(Harada等人，2002；Kirsch等人，1997；Neophytou等人，1997；Walsh等人，2001)虽然对LIF在眼睛中的调控表达知之甚少，但CNTF已被证明在损伤或应激后在视网膜中上调。(曹等人，1997；温氏等人，1995；温氏等人，1998)这种上调导致了一种假设，即gp130的激活是视网膜神经保护的内源性机制。为了支持这一假说，研究表明，通过将LIF或CNTF直接注射到眼内或通过转导细胞表达激活gp130，可以有效地保护视网膜神经元免受细胞死亡的影响。这包括长期暴露在持续光照下造成的细胞死亡和遗传性视网膜退行性突变(Bok等人，2002；Cayouette和Gravel，1997；LaVail等人，1998；LaVail等人，1992)。CNTF和LIF目前都处于治疗神经退行性疾病的临床试验中，包括肌萎缩侧索硬化症(Festoff，1996)和视网膜色素变性(www.Clinicaltrials.gov)。虽然CNTF和LIF在防止细胞死亡方面是有效的，但其机制尚未确定。
Leukemia inhibitory factor (LIF) is a member of the interleukin 6 (IL-6) family of cytokines, which also includes oncostatin-M, ciliary neurotrophic factor (CNTF), interleukin-11, and cardiotrophin-1. Members of this family are grouped together based on activation of a common tyrosine kinase receptor, gp130. (Ip et al, 1992) The expression of activating ligands of gp130, including LIF and CNTF, have been localized to Muller glial cells and microglial cells in the retina. (Harada et al, 2002; Kirsch et al, 1997; Neophytou et al, 1997; Walsh et al, 2001) While little is known about the regulated expression of LIF in the eye, CNTF has been shown to be up-regulated in the retina following injury or stress. (Cao et al, 1997; Wen et al, 1995; Wen et al, 1998) This up regulation has led to the hypothesis that activation of gp130 is an endogenous mechanism for neuroprotection in the retina. In support of this hypothesis, it has been shown that activating gp130 either by direct injections of LIF or CNTF into the eye or by their expression from transduced cells is effective at protecting retinal neurons from cell death. This includes cell death caused by prolonged exposure to constant light and inherited retinal degenerative mutations (Bok et al, 2002; Cayouette and Gravel, 1997; LaVail et al, 1998; LaVail et al, 1992). CNTF and LIF are both currently in clinical trials for the treatment of neurological degenerative disorders including amyotrophic lateral sclerosis (Festoff, 1996) and retinitis pigmentosa (www.clinicaltrials.gov). While CNTF and LIF are effective at preventing cell death, the mechanism has not yet been identified.