Connexin 43 contributes to differentiation of retinal pigment epithelial cells via cyclic AMP signaling
Connexin 43 contributes to differentiation of retinal pigment epithelial cells via cyclic AMP signaling
复制标题
DOI：
10.1016/j.bbrc.2007.11.159
复制
发表时间：
2008-02-08
影响因子：
3.1
通讯作者：
Morita, Ikuo
中科院分区：
文献类型：
--
作者：
Kojima, Ariko;Nakahama, Ken-ichi;Morita, Ikuo
视网膜色素上皮（RPE）细胞在支持神经感觉视网膜稳态的视觉系统中起重要作用。连接蛋白（Cx）43介导的缝隙连接细胞间通讯（GJIC）参与视网膜器官发生的调控，但Cx 43在RPE细胞分化中的作用尚不清楚。在这里，我们报告了Cx43参与RPE分化。在RPE细胞中敲低Cx43显著抑制分化，而Cx43过表达在去分化条件下成功诱导RPE细胞分化。从使用GJIC抑制剂和Cx43的C-末端截短突变体的实验中，清楚地表明Cx43对RPE细胞分化的调节不是由Cx43介导的GJIC引起的。cAMP拮抗剂可抑制Cx43过表达诱导的RPE细胞分化。相反，在去分化条件下，用毛喉素和磷酸二酯酶抑制剂咯利普兰处理诱导RPE细胞分化。这些发现表明Cx43通过cAMP信号通路促进RPE分化。(c)2007爱思唯尔公司All rights reserved.
Retinal pigment epithelium (RPE) cells play important roles in the visual system that supports neurosensory retina homeostasis. Connexin (Cx) 43-mediated gap-junctional intercellular communication (GJIC) participates in the regulation of retinal organogenesis, but much of the function of Cx43 on the differentiation of RPE cells is unclear. Here, we report the involvement of Cx43 in RPE differentiation. Knockdown of Cx43 in RPE cells dramatically inhibited the differentiation, whereas Cx43-overexpression successfully induced RPE cell differentiation under de-differentiation conditions. From the experiments using GJIC inhibitors and C-terminus-truncated mutant of Cx43, it was clearly demonstrated that the regulation of RPE cell differentiation by Cx43 did not result from Cx43-mediated GJIC. The RPE cell differentiation induced by Cx43-overexpression was abolished by a cAMP antagonist. In contrast, the treatment with forskolin and phosphodiesterase inhibitor rolipram induced RPE cell differentiation under de-differentiation conditions. These findings indicate that Cx43 contributes to RPE differentiation via cAMP signaling. (c) 2007 Elsevier Inc. All rights reserved.