HGF诱导的角质形成细胞迁移中SOCS3/CIS3对STAT3的负调控作用

SOCS3/CIS3 negative regulation of STAT3 in HGF-induced keratinocyte migration.

作者信息

Tokumaru Sho, Sayama Koji, Yamasaki Kenshi, Shirakata Yuji, Hanakawa Yasushi, Yahata Yoko, Dai Xiuju, Tohyama Mikiko, Yang Lujun, Yoshimura Akihiko, Hashimoto Koji

机构信息

Department of Dermatology, Ehime University School of Medicine, Ehime, Japan.

出版信息

Biochem Biophys Res Commun. 2005 Feb 4;327(1):100-5. doi: 10.1016/j.bbrc.2004.11.145.

DOI:10.1016/j.bbrc.2004.11.145

PMID:15629435

Abstract

Hepatocyte growth factor (HGF) is a potent mitogen for mature hepatocytes. Because HGF has strong effects on the motility of keratinocytes and is produced by fibroblasts, HGF is thought to regulate keratinocyte migration during wound healing. However, the intracellular signaling mechanism of HGF-induced keratinocyte migration is poorly understood. In this report, we clarify the roles of STAT3 and SOCS/CIS family in HGF-induced keratinocyte migration. HGF activated STAT3 and strongly induced keratinocyte migration. Transfection with the dominant-negative mutant of STAT3 almost completely abolished HGF-induced keratinocyte migration and STAT3 phosphorylation. Next, we studied the mechanisms that regulate STAT3 phosphorylation. HGF enhanced the expression of SOCS3/CIS3 by sixfold within 1h, but had minimum effect on SOCS1/JAB expression. Transfection with SOCS3/CIS3 almost completely abolished HGF-induced STAT3 phosphorylation and keratinocyte migration, indicating that SOCS3/CIS3 acts as a negative regulator of HGF-induced keratinocyte migration. In conclusion, SOCS3/CIS3 regulates HGF-induced keratinocyte migration by inhibiting STAT3 phosphorylation.

摘要

肝细胞生长因子（HGF）是成熟肝细胞的一种强效促有丝分裂原。由于HGF对角质形成细胞的运动具有强烈影响且由成纤维细胞产生，因此HGF被认为在伤口愈合过程中调节角质形成细胞的迁移。然而，HGF诱导角质形成细胞迁移的细胞内信号传导机制尚不清楚。在本报告中，我们阐明了STAT3和SOCS/CIS家族在HGF诱导的角质形成细胞迁移中的作用。HGF激活了STAT3并强烈诱导角质形成细胞迁移。用STAT3的显性负性突变体转染几乎完全消除了HGF诱导的角质形成细胞迁移和STAT3磷酸化。接下来，我们研究了调节STAT3磷酸化的机制。HGF在1小时内将SOCS3/CIS3的表达提高了6倍，但对SOCS1/JAB的表达影响最小。用SOCS3/CIS3转染几乎完全消除了HGF诱导的STAT3磷酸化和角质形成细胞迁移，表明SOCS3/CIS3作为HGF诱导的角质形成细胞迁移的负调节因子。总之，SOCS3/CIS3通过抑制STAT3磷酸化来调节HGF诱导的角质形成细胞迁移。