Kojima Ariko, Nakahama Ken-Ichi, Ohno-Matsui Kyoko, Shimada Noriaki, Mori Keisuke, Iseki Sachiko, Sato Tetsuji, Mochizuki Manabu, Morita Ikuo
Department of Cellular Physiological Chemistry, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
Biochem Biophys Res Commun. 2008 Feb 8;366(2):532-8. doi: 10.1016/j.bbrc.2007.11.159. Epub 2007 Dec 7.
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.
视网膜色素上皮（RPE）细胞在维持神经感觉视网膜内环境稳定的视觉系统中发挥着重要作用。连接蛋白（Cx）43介导的间隙连接细胞间通讯（GJIC）参与视网膜器官发生的调控，但Cx43在RPE细胞分化中的大部分功能尚不清楚。在此，我们报道了Cx43参与RPE细胞分化。RPE细胞中Cx43的敲低显著抑制了分化，而在去分化条件下，Cx43的过表达成功诱导了RPE细胞分化。通过使用GJIC抑制剂和Cx43的C末端截短突变体进行的实验清楚地表明，Cx43对RPE细胞分化的调控并非源于Cx43介导的GJIC。Cx43过表达诱导的RPE细胞分化被一种cAMP拮抗剂消除。相反，用福司可林和磷酸二酯酶抑制剂咯利普兰处理在去分化条件下诱导了RPE细胞分化。这些发现表明，Cx43通过cAMP信号通路促进RPE细胞分化。
