Abstract

Nephronectin (Npnt) is an extracellular matrix protein and ligand of integrin α8β1 known to promote differentiation of osteoblasts. A search for factors that regulate Npnt gene expression in osteoblasts revealed that phorbol 12-myristate 13-acetate (PMA), which activates protein kinase C (PKC), had a strong effect to suppress that expression. Research was then conducted to elucidate the signaling pathway responsible for regulation of Npnt gene expression by PMA in osteoblasts. Treatment of MC3T3-E1 cells with PMA suppressed cell differentiation and Npnt gene expression. Effects were noted at a low concentration of PMA, and were time- and dose-dependent. Furthermore, treatment with the PKC signal inhibitor Gö6983 inhibited down-regulation of Npnt expression, while transfection with small interfering RNA (siRNA) of PKCα, c-Jun, and c-Fos suppressed that down-regulation. The present results suggest regulation of Npnt gene expression via the PKCα and c-Jun/c-Fos pathway.

Details

Title
Phorbol-12-myristate 13-acetate inhibits Nephronectin gene expression via Protein kinase C alpha and c-Jun/c-Fos transcription factors
Author
Kinoshita Mitsuhiro 1 ; Yamada Atsushi 1 ; Kiyohito, Sasa 1 ; Ikezaki Kaori 2 ; Shirota Tatsuo 3 ; Kamijo Ryutaro 1 

 Showa University, Department of Biochemistry, School of Dentistry, Tokyo, Japan (GRID:grid.410714.7) (ISNI:0000 0000 8864 3422) 
 Showa University, Department of Biochemistry, School of Dentistry, Tokyo, Japan (GRID:grid.410714.7) (ISNI:0000 0000 8864 3422); Showa University, Department of Oral and Maxillofacial Surgery, School of Dentistry, Tokyo, Japan (GRID:grid.410714.7) (ISNI:0000 0000 8864 3422) 
 Showa University, Department of Oral and Maxillofacial Surgery, School of Dentistry, Tokyo, Japan (GRID:grid.410714.7) (ISNI:0000 0000 8864 3422) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2581617700
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.