Involvement of PI3K and PKA pathways in mouse tongue epithelial differentiation

Jae-Kwang Jung; Hye-In Jung; Sanjiv Neupane; Ki-Rim Kim; Ji-Youn Kim; Hitoshi Yamamoto; Sung-Won Cho; Youngkyun Lee; Hong-In Shin; Wern-Joo Sohn; Jae-Young Kim

doi:10.1016/j.acthis.2016.11.013

Involvement of PI3K and PKA pathways in mouse tongue epithelial differentiation

Acta Histochem. 2017 Jan;119(1):92-98. doi: 10.1016/j.acthis.2016.11.013. Epub 2016 Dec 8.

Authors

Affiliations

¹ Department of Oral Medicine, School of Dentistry, IHBR, Kyungpook National University, Daegu, South Korea.
² Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu, South Korea.
³ Department of Dental Hygiene, IHBR, Kyungpook National University, Daegu, South Korea.
⁴ Department of Dental Hygiene, Gachon University College of Health Science, Incheon, Seoul, South Korea.
⁵ Department of Histology and Developmental Biology, Tokyo Dental College, Tokyo, Japan.
⁶ Division in Anatomy and Developmental Biology, Department of Oral Biology, Yonsei University College of Dentistry, Seoul, South Korea.
⁷ Department of Oral Pathology and Regenerative Medicine, School of Dentistry, Daegu, South Korea.
⁸ IHBR, Kyungpook National University, Daegu, South Korea. Electronic address: undine75@gmail.com.
⁹ Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu, South Korea. Electronic address: jykim91@knu.ac.kr.

PMID: 27939449
DOI: 10.1016/j.acthis.2016.11.013

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.

Keywords: Epithelial differentiation; Keratinization; Multiple cell layer formation; PI3K; PKA; Tongue barrier formation.

MeSH terms

Animals
Butadienes / pharmacology
Cell Differentiation / drug effects
Cell Proliferation / drug effects
Chromones / pharmacology
Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
Cyclic AMP-Dependent Protein Kinases / genetics
Cyclic AMP-Dependent Protein Kinases / metabolism*
Embryo, Mammalian
Epithelial Cells / drug effects
Epithelial Cells / metabolism
Epithelial Cells / ultrastructure*
Epithelial-Mesenchymal Transition / drug effects
Fixatives
Flavonoids / pharmacology
Formaldehyde
Gene Expression Regulation, Developmental
Isoquinolines / pharmacology
Ki-67 Antigen / genetics
Ki-67 Antigen / metabolism
Mice
Mice, Inbred ICR
Morpholines / pharmacology
Nitriles / pharmacology
Organ Culture Techniques
Paraffin Embedding
Phosphatidylinositol 3-Kinases / genetics
Phosphatidylinositol 3-Kinases / metabolism*
Phosphoinositide-3 Kinase Inhibitors
Polymers
Signal Transduction*
Sulfonamides / pharmacology
Tongue / drug effects
Tongue / growth & development
Tongue / metabolism
Tongue / ultrastructure*

Substances

Butadienes
Chromones
Fixatives
Flavonoids
Isoquinolines
Ki-67 Antigen
Mki67 protein, mouse
Morpholines
Nitriles
Phosphoinositide-3 Kinase Inhibitors
Polymers
Sulfonamides
U 0126
Formaldehyde
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Cyclic AMP-Dependent Protein Kinases
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
paraform