Cdc42 inhibits ERK-mediated collagenase-1 (MMP-1) expression in collagen-activated human keratinocytes

The Journal of Investigative Dermatology
Maryam G RohaniW C Parks

Abstract

Following injury, keratinocytes switch gene expression programs from the one that promotes differentiation to the one that supports migration. A common feature of human wounds and ulcerations of any form is the expression of matrix metalloproteinase 1 (MMP-1; collagenase-1) by leading-edge basal keratinocytes migrating across the dermal or provisional matrix. Induction of MMP-1 occurs by signaling from the α2β1 integrin in contact with dermal fibrillar type I collagen, and the activity of MMP-1 is required for human keratinocytes to migrate on collagen. Thus, MMP-1 serves a critical role in the repair of damaged human skin. Here, we evaluated the mechanisms controlling MMP-1 expression in primary human keratinocytes from neonatal foreskin and adult female skin. Our results demonstrate that shortly following contact with type I collagen extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase were markedly activated, whereas c-Jun N-terminal kinase (JNK) phosphorylation remained at basal levels. ERK inhibition markedly blocked collagen-stimulated MMP-1 expression in keratinocytes. In contrast, inhibiting p38 or JNK pathways had no effect on MMP-1 production. Moreover, investigating the role of Rho GTP...Continue Reading

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Citations

May 29, 2015·The Journal of Investigative Dermatology·Hong ChengYumin Xia
Mar 17, 2015·Matrix Biology : Journal of the International Society for Matrix Biology·Maryam G Rohani, William C Parks
Feb 16, 2016·The British Journal of Dermatology·X LiuY Xia
Feb 9, 2020·International Journal of Molecular Sciences·Georgia NikoloudakiDouglas W Hamilton
Aug 13, 2015·Experimental Dermatology·Hong ChengYumin Xia
Dec 20, 2018·Frontiers in Immunology·Maryam G RohaniWilliam C Parks
Dec 9, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Chia-Ying HsuSung-Liang Yu
Aug 20, 2021·Mechanisms of Ageing and Development·Tanya PulidoFatouma Alimirah

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Methods Mentioned

BETA
GTPases
motility assay
GTPase
PMA
biopsies
circumcision
ELISA
protein assay
Assay
transfection

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