title: Connexin 43 contributes to differentiation of retinal pigment epithelial cells via cyclic AMP signaling.
abstract: 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.
authors: Department of Cellular Physiological Chemistry, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors: Ariko
authors: A
authors: Kojima
authors: Ken-Ichi
authors: K
authors: Nakahama
authors: Kyoko
authors: K
authors: Ohno-Matsui
authors: Noriaki
authors: N
authors: Shimada
authors: Keisuke
authors: K
authors: Mori
authors: Sachiko
authors: S
authors: Iseki
authors: Tetsuji
authors: T
authors: Sato
authors: Manabu
authors: M
authors: Mochizuki
authors: Ikuo
authors: I
authors: Morita
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D010857:Pigment Epithelium of Eye / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D018031:Connexin 43; D000242:Cyclic AMP