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Connexin 43 contributes to differentiation of retinal pigment epithelial cells via cyclic AMP signaling |
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| Authors: | Kojima Ariko Nakahama Ken-Ichi Ohno-Matsui Kyoko Shimada Noriaki Mori Keisuke Iseki Sachiko Sato Tetsuji Mochizuki Manabu Morita Ikuo |
| Institution: | a Department of Cellular Physiological Chemistry, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan b Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan c Department of Ophthalmology, Saitama Medical University, Faculty of Medicine, 38 Morohongo, Moroyama, Iruma, Saitama 350-0495, Japan d Department of Molecular Craniofacial Embryology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan e Department of Anatomy II, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan |
| 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. |
| Keywords: | RPE retinal pigment epithelium Cx connexin GJIC gap-junctional intercellular communication CNV choroidal neovascularization AMD age-related macular degeneration shRNA short hairpin RNA rCx43 rat connexin 43 bFGF basic FGF CRALBP cellular retinaldehyde-binding protein TRP-2 tyrosinase-related protein-2 PEDF pigment epithelium-derived factor 18β-GA 18β-glycyrrhetinic acid GA glycyrrhizic acid |
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