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bFGF Regulates PI3-Kinase-Rac1-JNK Pathway and Promotes Fibroblast Migration in Wound Healing

Fibroblast proliferation and migration play important roles in wound healing. bFGF is known to promote both fibroblast proliferation and migration during the process of wound healing. However, the signal transduction of bFGF-induced fibroblast migration is still unclear, because bFGF can affect both...

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Autores principales: Kanazawa, Shigeyuki, Fujiwara, Toshihiro, Matsuzaki, Shinsuke, Shingaki, Kenta, Taniguchi, Manabu, Miyata, Shingo, Tohyama, Masaya, Sakai, Yasuo, Yano, Kenji, Hosokawa, Ko, Kubo, Tateki
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923192/
https://www.ncbi.nlm.nih.gov/pubmed/20808927
http://dx.doi.org/10.1371/journal.pone.0012228
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author Kanazawa, Shigeyuki
Fujiwara, Toshihiro
Matsuzaki, Shinsuke
Shingaki, Kenta
Taniguchi, Manabu
Miyata, Shingo
Tohyama, Masaya
Sakai, Yasuo
Yano, Kenji
Hosokawa, Ko
Kubo, Tateki
author_facet Kanazawa, Shigeyuki
Fujiwara, Toshihiro
Matsuzaki, Shinsuke
Shingaki, Kenta
Taniguchi, Manabu
Miyata, Shingo
Tohyama, Masaya
Sakai, Yasuo
Yano, Kenji
Hosokawa, Ko
Kubo, Tateki
author_sort Kanazawa, Shigeyuki
collection PubMed
description Fibroblast proliferation and migration play important roles in wound healing. bFGF is known to promote both fibroblast proliferation and migration during the process of wound healing. However, the signal transduction of bFGF-induced fibroblast migration is still unclear, because bFGF can affect both proliferation and migration. Herein, we investigated the effect of bFGF on fibroblast migration regardless of its effect on fibroblast proliferation. We noticed involvement of the small GTPases of the Rho family, PI3-kinase, and JNK. bFGF activated RhoA, Rac1, PI3-kinase, and JNK in cultured fibroblasts. Inhibition of RhoA did not block bFGF-induced fibroblast migration, whereas inhibition of Rac1, PI3-kinase, or JNK blocked the fibroblast migration significantly. PI3-kinase-inhibited cells down-regulated the activities of Rac1 and JNK, and Rac1-inhibited cells down-regulated JNK activity, suggesting that PI3-kinase is upstream of Rac1 and that JNK is downstream of Rac1. Thus, we concluded that PI3-kinase, Rac1, and JNK were essential for bFGF-induced fibroblast migration, which is a novel pathway of bFGF-induced cell migration.
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spelling pubmed-29231922010-08-31 bFGF Regulates PI3-Kinase-Rac1-JNK Pathway and Promotes Fibroblast Migration in Wound Healing Kanazawa, Shigeyuki Fujiwara, Toshihiro Matsuzaki, Shinsuke Shingaki, Kenta Taniguchi, Manabu Miyata, Shingo Tohyama, Masaya Sakai, Yasuo Yano, Kenji Hosokawa, Ko Kubo, Tateki PLoS One Research Article Fibroblast proliferation and migration play important roles in wound healing. bFGF is known to promote both fibroblast proliferation and migration during the process of wound healing. However, the signal transduction of bFGF-induced fibroblast migration is still unclear, because bFGF can affect both proliferation and migration. Herein, we investigated the effect of bFGF on fibroblast migration regardless of its effect on fibroblast proliferation. We noticed involvement of the small GTPases of the Rho family, PI3-kinase, and JNK. bFGF activated RhoA, Rac1, PI3-kinase, and JNK in cultured fibroblasts. Inhibition of RhoA did not block bFGF-induced fibroblast migration, whereas inhibition of Rac1, PI3-kinase, or JNK blocked the fibroblast migration significantly. PI3-kinase-inhibited cells down-regulated the activities of Rac1 and JNK, and Rac1-inhibited cells down-regulated JNK activity, suggesting that PI3-kinase is upstream of Rac1 and that JNK is downstream of Rac1. Thus, we concluded that PI3-kinase, Rac1, and JNK were essential for bFGF-induced fibroblast migration, which is a novel pathway of bFGF-induced cell migration. Public Library of Science 2010-08-17 /pmc/articles/PMC2923192/ /pubmed/20808927 http://dx.doi.org/10.1371/journal.pone.0012228 Text en Kanazawa et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kanazawa, Shigeyuki
Fujiwara, Toshihiro
Matsuzaki, Shinsuke
Shingaki, Kenta
Taniguchi, Manabu
Miyata, Shingo
Tohyama, Masaya
Sakai, Yasuo
Yano, Kenji
Hosokawa, Ko
Kubo, Tateki
bFGF Regulates PI3-Kinase-Rac1-JNK Pathway and Promotes Fibroblast Migration in Wound Healing
title bFGF Regulates PI3-Kinase-Rac1-JNK Pathway and Promotes Fibroblast Migration in Wound Healing
title_full bFGF Regulates PI3-Kinase-Rac1-JNK Pathway and Promotes Fibroblast Migration in Wound Healing
title_fullStr bFGF Regulates PI3-Kinase-Rac1-JNK Pathway and Promotes Fibroblast Migration in Wound Healing
title_full_unstemmed bFGF Regulates PI3-Kinase-Rac1-JNK Pathway and Promotes Fibroblast Migration in Wound Healing
title_short bFGF Regulates PI3-Kinase-Rac1-JNK Pathway and Promotes Fibroblast Migration in Wound Healing
title_sort bfgf regulates pi3-kinase-rac1-jnk pathway and promotes fibroblast migration in wound healing
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923192/
https://www.ncbi.nlm.nih.gov/pubmed/20808927
http://dx.doi.org/10.1371/journal.pone.0012228
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