Mimura Yoshihiro, Ihn Hironobu, Jinnin Masatoshi, Asano Yoshihide, Yamane Kenichi, Tamaki Kunihiko
Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Matrix Biol. 2006 May;25(4):202-12. doi: 10.1016/j.matbio.2005.12.002. Epub 2006 Jan 18.
EGF and type I collagen are known to play important roles in wound healing. In the present study, we demonstrated that EGF down-regulates the expression of type I procollagen protein as well as alpha2(I) collagen mRNA in cultured human dermal fibroblasts. EGF induced the degradation of type I procollagen protein in conditioned medium through the up-regulation of MMP-1 expression. EGF down-regulated alpha2(I) mRNA expression partially at the post-transcriptional level by reducing the mRNA stability. In contrast, EGF up-regulated MMP-1 mRNA expression mostly at the transcriptional level, in that it had a stimulatory effect on MMP-1 promoter activity, but no effect on MMP-1 mRNA stability. The MEK/ERK signaling pathway was shown to be involved in EGF-mediated type I collagen and MMP-1 expression.
已知表皮生长因子(EGF)和I型胶原蛋白在伤口愈合中发挥重要作用。在本研究中,我们证明,在培养的人皮肤成纤维细胞中,EGF可下调I型前胶原蛋白蛋白以及α2(I)胶原蛋白mRNA的表达。EGF通过上调基质金属蛋白酶-1(MMP-1)的表达,诱导条件培养基中I型前胶原蛋白蛋白的降解。EGF通过降低mRNA稳定性,在转录后水平部分下调α2(I)mRNA的表达。相反,EGF大多在转录水平上调MMP-1 mRNA的表达,因为它对MMP-1启动子活性有刺激作用,但对MMP-1 mRNA稳定性没有影响。丝裂原活化蛋白激酶/细胞外信号调节激酶(MEK/ERK)信号通路被证明参与EGF介导的I型胶原蛋白和MMP-1的表达。