Connexin 43 Is Necessary for Salivary Gland Branching Morphogenesis and FGF10-induced ERK1/2 Phosphorylation

被引：26

作者：

Yamada, Aya ^{[1
]}

Futagi, Masaharu ^{[1
]}

Fukumoto, Emiko ^{[1
]}

Saito, Kan ^{[1
]}

Yoshizaki, Keigo ^{[3
]}

Ishikawa, Masaki ^{[2
]}

Arakaki, Makiko ^{[1
]}

Hino, Ryoko ^{[1
]}

Sugawara, Yu ^{[1
]}

Ishikawa, Momoko ^{[1
]}

Naruse, Masahiro ^{[1
]}

Miyazaki, Kanako ^{[3
]}

Nakamura, Takashi ^{[1
]}

Fukumoto, Satoshi ^{[1
]}

机构：

[1] Tohoku Univ, Grad Sch Dent, Dept Oral Hlth & Dev Sci, Div Pediat Dent, Sendai, Miyagi 9808575, Japan

[2] Tohoku Univ, Grad Sch Dent, Dept Restorat Dent, Operat Dent, Sendai, Miyagi 9808575, Japan

[3] Kyushu Univ, Fac Dent Sci, Div Oral Hlth Growth & Dev, Div Orthodont, Fukuoka 8128582, Japan

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2016年 / 291卷 / 02期

关键词：

IP3 RECEPTOR/CA2+ CHANNEL; GAP-JUNCTION CHANNELS; OCULODENTODIGITAL DYSPLASIA; DIFFERENTIAL EXPRESSION; GJA1; MUTATIONS; PROLIFERATION; HEMICHANNELS; DYSFUNCTION; PHENOTYPE; GROWTH;

D O I：

10.1074/jbc.M115.674663

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cell-cell interaction via the gap junction regulates cell growth and differentiation, leading to formation of organs of appropriate size and quality. To determine the role of connexin43 in salivary gland development, we analyzed its expression in developing submandibular glands (SMGs). Connexin43 (Cx43) was found to be expressed in salivary gland epithelium. In ex vivo organ cultures of SMGs, addition of the gap junctional inhibitors 18 alpha-glycyrrhetinic acid (18 alpha-GA) and oleamide inhibited SMG branching morphogenesis, suggesting that gap junctional communication contributes to salivary gland development. In Cx43(-/-) salivary glands, submandibular and sublingual gland size was reduced as compared with those from heterozygotes. The expression of Pdgfa, Pdgfb, Fgf7, and Fgf10, which induced branching of SMGs in Cx43(-/-) samples, were not changed as compared with those from heterozygotes. Furthermore, the blocking peptide for the hemichannel and gap junction channel showed inhibition of terminal bud branching. FGF10 induced branching morphogenesis, while it did not rescue the Cx43(-/-) phenotype, thus Cx43 may regulate FGF10 signaling during salivary gland development. FGF10 is expressed in salivary gland mesenchyme and regulates epithelial proliferation, and was shown to induce ERK1/2 phosphorylation in salivary epithelial cells, while ERK1/2 phosphorylation in HSY cells was dramatically inhibited by 18 alpha-GA, a Cx43 peptide or siRNA. On the other hand, PDGF-AA and PDGF-BB separately induced ERK1/2 phosphorylation in primary cultured salivary mesenchymal cells regardless of the presence of 18 alpha-GA. Together, our results suggest that Cx43 regulates FGF10-induced ERK1/2 phosphorylation in salivary epithelium but not in mesenchyme during the process of SMG branching morphogenesis.

引用

页码：904 / 912

页数：9

共 35 条

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