Epidermal growth factor affects the synthesis and degradation of type I collagen in cultured human dermal fibroblasts. 2006

Yoshihiro Mimura, and Hironobu Ihn, and Masatoshi Jinnin, and Yoshihide Asano, and Kenichi Yamane, and Kunihiko Tamaki
Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

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.

UI MeSH Term Description Entries
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D004815 Epidermal Growth Factor A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form. EGF,Epidermal Growth Factor-Urogastrone,Urogastrone,Human Urinary Gastric Inhibitor,beta-Urogastrone,Growth Factor, Epidermal,Growth Factor-Urogastrone, Epidermal,beta Urogastrone
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014945 Wound Healing Restoration of integrity to traumatized tissue. Healing, Wound,Healings, Wound,Wound Healings
D020405 Dermis A layer of vascularized connective tissue underneath the EPIDERMIS. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are SWEAT GLANDS; HAIR FOLLICLES; and SEBACEOUS GLANDS. Corium
D020935 MAP Kinase Signaling System An intracellular signaling system involving the mitogen-activated protein kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade. MAP Kinase Cascade,MAP Kinase Module,MAP Kinase Signaling Cascade,MAP Kinase Signaling Pathway,MAP Kinase Signaling Pathways,ERK Pathway,ERK Signal Tranduction Pathway,ERK1 and ERK2 Pathway,ERK1-2 Pathway,JNK Pathway,JNK Signaling Pathway,MAP Kinase Modules,MAP Kinase Signaling Cascades,MEK-ERK Pathway,p38 Kinase Pathway,p38 Kinase Signaling Pathway,Cascade, MAP Kinase,ERK Pathways,ERK1 2 Pathway,ERK1-2 Pathways,JNK Pathways,JNK Signaling Pathways,Kinase Cascade, MAP,Kinase Pathway, p38,Kinase Pathways, p38,MAP Kinase Cascades,MEK ERK Pathway,MEK-ERK Pathways,Module, MAP Kinase,Pathway, ERK,Pathway, ERK1-2,Pathway, JNK,Pathway, JNK Signaling,Pathway, MEK-ERK,Pathway, p38 Kinase,Pathways, ERK,Pathways, ERK1-2,Pathways, JNK,Pathways, JNK Signaling,Pathways, MEK-ERK,Pathways, p38 Kinase,Signaling Pathway, JNK,Signaling Pathways, JNK,p38 Kinase Pathways
D024042 Collagen Type I The most common form of fibrillar collagen. It is a major constituent of bone (BONE AND BONES) and SKIN and consists of a heterotrimer of two alpha1(I) and one alpha2(I) chains. Type 1 Collagen,Type I Collagen,Collagen, Type 1,Collagen, Type I

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