Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ohta-ku, Tokyo, 145-8515, Japan.
Sci Rep. 2021 Oct 13;11(1):20360. doi: 10.1038/s41598-021-00034-x.
Nephronectin (Npnt) is an extracellular matrix protein and ligand of integrin αβ 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.
纤连蛋白（Npnt）是一种细胞外基质蛋白和整合素αβ的配体，已知可促进成骨细胞分化。在寻找调节成骨细胞中 Npnt 基因表达的因素时，发现佛波醇 12-肉豆蔻酸 13-醋酸盐（PMA）可激活蛋白激酶 C（PKC），对抑制该表达有很强的作用。随后进行了研究以阐明 PMA 在成骨细胞中调节 Npnt 基因表达的信号通路。用 PMA 处理 MC3T3-E1 细胞可抑制细胞分化和 Npnt 基因表达。在低浓度 PMA 时即可观察到作用，且呈时间和剂量依赖性。此外，用 PKC 信号抑制剂 Gö6983 处理可抑制 Npnt 表达的下调，而用 PKCα、c-Jun 和 c-Fos 的小干扰 RNA（siRNA）转染可抑制这种下调。本研究结果提示通过 PKCα 和 c-Jun/c-Fos 途径调节 Npnt 基因表达。
