Phorbol-12-myristate 13-acetate inhibits Nephronectin gene expression via Protein kinase C alpha and c-Jun/c-Fos transcription factors

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.

Caudatin attenuates inflammatory reaction by suppressing JNK/AP-1/NF-κB/caspase-1 pathways in activated HMC-1 cells

“…PMA, which activates protein kinase C (PKC), induces the activation of JNK, AP-1, and NF-κB (Kinoshita et al, 2021 ; Le et al, 2014 ). In the current investigation, caudatin (50 μM) alone raised the expression of AP-1 and p65 and the phosphorylation of JNK and IκBα.…”