bFGF regulates PI3-kinase-Rac1-JNK pathway and promotes fibroblast migration in wound healing.
bFGF regulates PI3-kinase-Rac1-JNK pathway and promotes fibroblast migration in wound healing.
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DOI：
10.1371/journal.pone.0012228
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发表时间：
2010-08-17
期刊：
影响因子：
3.7
通讯作者：
Kubo T
中科院分区：
文献类型：
--
作者：
Kanazawa S;Fujiwara T;Matsuzaki S;Shingaki K;Taniguchi M;Miyata S;Tohyama M;Sakai Y;Yano K;Hosokawa K;Kubo T
成纤维细胞的增殖和迁移在创伤愈合中起重要作用。已知bFGF在伤口愈合过程中促进成纤维细胞增殖和迁移。然而，bFGF诱导的成纤维细胞迁移的信号转导仍然不清楚，因为bFGF可以影响增殖和迁移。在此，我们研究了bFGF对成纤维细胞迁移的影响，而不管其对成纤维细胞增殖的影响。我们注意到Rho家族的小GTP酶、PI 3-激酶和JNK的参与。在培养的成纤维细胞中，bFGF激活RhoA、Rac 1、PI 3-激酶和JNK。抑制RhoA并不能阻断bFGF诱导的成纤维细胞迁移，而抑制Rac 1、PI 3-激酶或JNK则显著阻断了成纤维细胞迁移。PI 3激酶抑制细胞下调Rac 1和JNK的活性，Rac 1抑制细胞下调JNK的活性，表明PI 3激酶是Rac 1的上游，JNK是Rac 1的下游。因此，我们得出结论，PI 3激酶，Rac 1，JNK是必不可少的bFGF诱导的成纤维细胞迁移，这是一个新的途径bFGF诱导的细胞迁移。
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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DOI：
10.1083/jcb.139.1.279
发表时间：
1997-10-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Jones PL;Crack J;Rabinovitch M
通讯作者：
Rabinovitch M
影响因子：
9.2
作者：
Higuchi, M;Masuyama, N;Gotoh, Y
通讯作者：
Gotoh, Y
影响因子：
21.3
作者：
Andrew, Natalie;Insall, Robert H.
通讯作者：
Insall, Robert H.
影响因子：
4
作者：
Liu, GZ;Eskin, SG;Mikos, AG
通讯作者：
Mikos, AG
影响因子：
20.1
作者：
Chang, YZ;Ceacareanu, B;Hassid, A
通讯作者：
Hassid, A