title: Involvement of PI3K and PKA pathways in mouse tongue epithelial differentiation.
abstract: In mice, tongue epithelial differentiation is mainly regulated by the interactions among various signalling molecules including Fgf signalling pathways. However, the subsequent signalling modulations for epithelial maturation, initiated by Fgf signalling, remain to be elucidated. Therefore, we employed an in vitro tongue organ cultivation system along with the applications of various pharmacological inhibitors against the intracellular signalling molecules of Fgf signalling pathways, including H89, LY294002, PD98059, and U0126. Following treatments with LY294002 and H89, inhibitors for PI3K and PKA, respectively, the decreased thickness of the tongue epithelium was observed along with the alteration in cell proliferative and apoptotic patterns. Meanwhile, cultivated tongues treated with MEK inhibitor U0126 or PD98059 showed significantly decreased cell proliferation in the tongue epithelium and the mesenchyme. Based on these results, we suggest that the tongue epithelium is differentiated into multiple epithelial cell layers via the PI3K and PKA pathways in tissue-specific manner during the epithelial-mesenchymal interactions.
authors.affiliation: Department of Oral Medicine, School of Dentistry, IHBR, Kyungpook National University, Daegu, South Korea.
authors.forename: Jae-Kwang
authors.initials: JK
authors.lastname: Jung
authors.affiliation: Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu, South Korea.
authors.forename: Hye-In
authors.initials: HI
authors.lastname: Jung
authors.affiliation: Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu, South Korea.
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Neupane
authors.affiliation: Department of Dental Hygiene, IHBR, Kyungpook National University, Daegu, South Korea.
authors.forename: Ki-Rim
authors.initials: KR
authors.lastname: Kim
authors.affiliation: Department of Dental Hygiene, Gachon University College of Health Science, Incheon, Seoul, South Korea.
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Histology and Developmental Biology, Tokyo Dental College, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Division in Anatomy and Developmental Biology, Department of Oral Biology, Yonsei University College of Dentistry, Seoul, South Korea.
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu, South Korea.
authors.forename: Youngkyun
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Oral Pathology and Regenerative Medicine, School of Dentistry, Daegu, South Korea.
authors.forename: Hong-In
authors.initials: HI
authors.lastname: Shin
authors.affiliation: IHBR, Kyungpook National University, Daegu, South Korea. Electronic address: undine75@gmail.com.
authors.forename: Wern-Joo
authors.initials: WJ
authors.lastname: Sohn
authors.affiliation: Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu, South Korea. Electronic address: jykim91@knu.ac.kr.
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Kim
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005404:Fixatives; D005419:Flavonoids / Q000494:pharmacology; D005557:Formaldehyde; D018507:Gene Expression Regulation, Developmental; D007546:Isoquinolines / Q000494:pharmacology; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D009924:Organ Culture Techniques; D016612:Paraffin Embedding; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011108:Polymers; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology; D014059:Tongue / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure*
chemical_list: D002070:Butadienes; D002867:Chromones; D017868:Cyclic AMP-Dependent Protein Kinases; D005404:Fixatives; D005419:Flavonoids; D005557:Formaldehyde; D007546:Isoquinolines; D019394:Ki-67 Antigen; D009025:Morpholines; D009570:Nitriles; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011108:Polymers; D013449:Sulfonamides; C498355:Mki67 protein, mouse; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; C003043:paraform
keywords: Epithelial differentiation; Keratinization; Multiple cell layer formation; PI3K; PKA; Tongue barrier formation