SOCS3/CIS3 negative regulation of STAT3 in HGF-induced keratinocyte migration
SOCS3/CIS3 negative regulation of STAT3 in HGF-induced keratinocyte migration
复制标题
DOI：
10.1016/j.bbrc.2004.11.145
复制
发表时间：
2005-02-04
影响因子：
3.1
通讯作者：
Hashimoto, K
中科院分区：
文献类型：
--
作者：
Tokumaru, S;Sayama, K;Hashimoto, K
肝细胞生长因子（HGF）是成熟肝细胞的一种强有力的有丝分裂原。由于HGF对角质形成细胞的运动性具有强烈的影响并且由成纤维细胞产生，因此认为HGF在伤口愈合期间调节角质形成细胞的迁移。然而，HGF诱导的角质形成细胞迁移的细胞内信号传导机制知之甚少。在这篇报道中，我们阐明了STAT 3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STAT 3并强烈诱导角质形成细胞迁移。STAT 3显性负突变体的转染几乎完全消除了HGF诱导的角质形成细胞迁移和STAT 3磷酸化。接下来，我们研究了调节STAT 3磷酸化的机制。HGF使SOCS 3/CIS 3的表达在1 h内增加了6倍，但对SOCS 1/JAB的表达影响最小。用SOCS 3/CIS 3转染几乎完全消除了HGF诱导的STAT 3磷酸化和角质形成细胞迁移，表明SOCS 3/CIS 3作为HGF诱导的角质形成细胞迁移的负调节剂。总之，SOCS 3/CIS 3通过抑制STAT 3磷酸化调节HGF诱导的角质形成细胞迁移。(C)2004年爱思唯尔公司All rights reserved.
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 1 h, 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. (C) 2004 Elsevier Inc. All rights reserved.