Fibroblast Growth Factor 2 Suppresses the Expression of C-C Motif Chemokine 11 Through the C-Jun N-terminal Kinase Pathway in Human Dental Pulp-derived Mesenchymal Stem Cells

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2021 Oct 18

PMID 34659502

Citations 3

Authors

Rika Kurogoushi

Tomokazu Hasegawa

Yuki Akazawa

Kokoro Iwata

Asuna Sugimoto

Kimiko Yamaguchi-Ueda

Aya Miyazaki

Anrizandy Narwidina

Keita Kawarabayashi

Takamasa Kitamura

Hiroshi Nakagawa

Tomonori Iwasaki

Tsutomu Iwamoto

Affiliations

Soon will be listed here.

Abstract

The regulation of the mesenchymal stem cell (MSC) programming mechanism promises great success in regenerative medicine. Tissue regeneration has been associated not only with the differentiation of MSCs, but also with the microenvironment of the stem cell niche that involves various cytokines and immune cells in the tissue regeneration site. In the present study, fibroblast growth factor 2 (FGF2), the principal growth factor for tooth development, dental pulp homeostasis and dentin repair, was reported to affect the expression of cytokines in human dental pulp-derived MSCs. FGF2 significantly inhibited the expression of chemokine C-C motif ligand 11 (CCL11) in a time- and dose-dependent manner in the SDP11 human dental pulp-derived MSC line. This inhibition was diminished following treatment with the AZD4547 FGF receptor (FGFR) inhibitor, indicating that FGF2 negatively regulated the expression of CCL11 in SDP11 cells. Furthermore, FGF2 activated the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinases (JNK) in SDP11 cells. The mechanism of the FGFR-downstream signaling pathway was then studied using the SB203580, U0126 and SP600125 inhibitors for p38 MAPK, ERK1/2, and JNK, respectively. Interestingly, only treatment with SP600125 blocked the FGF2-mediated suppression of CCL11. The present results suggested that FGF2 regulated the expression of cytokines and suppressed the expression of CCL11 via the JNK signaling pathway in human dental pulp-derived MSCs. The present findings could provide important insights into the association of FGF2 and CCL11 in dental tissue regeneration therapy.

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