Hypoxia-induced epithelial-to-mesenchymal transition mediates fibroblast abnormalities via EKR activation in cutaneous wound healing

Jihee Kim, Bomi Kim, Soo Min Kim, Chae Eun Yang, Seung Yong Song, Won Jai Lee, JuHee Lee

Research output: Contribution to journalArticle

Abstract

Previous studies described the involvement of extracellular signal-related kinase (ERK) in systemic fibrotic diseases, but the role of ERK in cutaneous scarring is unknown. Although hypoxia drives tissue fibrosis by activating hypoxia-inducible factor-1α (HIF-1α), the specific roles of hypoxia and associated ERK phosphorylation in abnormal fibroblast activity during cutaneous scarring are unclear. Here, we investigated whether pathologic myofibroblast-like keloid fibroblast activity is promoted by hypoxia-induced epithelial–mesenchymal transition mediated by ERK activation. ERK phosphorylation was significantly increased in keloid tissue and fibroblasts. Human dermal fibroblasts cultured under hypoxia (1% O2) expressed phosphorylated ERK and exhibited activation of p38 mitogen-activated protein kinase signaling. Hypoxic human dermal fibroblasts showed increased protein and mRNA levels of epithelial–mesenchymal transition markers. Furthermore, administration of an ERK inhibitor (SCH772984) reduced the hypoxia-induced elevation of collagen type I levels in human dermal fibroblasts. Therefore, ERK may be a promising therapeutic target in profibrogenic diseases.

Original languageEnglish
Article number2546
JournalInternational journal of molecular sciences
Volume20
Issue number10
DOIs
Publication statusPublished - 2019 May 2

Fingerprint

wound healing
Epithelial-Mesenchymal Transition
hypoxia
abnormalities
fibroblasts
Fibroblasts
Wound Healing
Phosphotransferases
Chemical activation
activation
Skin
Phosphorylation
Keloid
phosphorylation
Tissue
Cicatrix
Proteins
proteins
Collagen
Hypoxia-Inducible Factor 1

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

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title = "Hypoxia-induced epithelial-to-mesenchymal transition mediates fibroblast abnormalities via EKR activation in cutaneous wound healing",
abstract = "Previous studies described the involvement of extracellular signal-related kinase (ERK) in systemic fibrotic diseases, but the role of ERK in cutaneous scarring is unknown. Although hypoxia drives tissue fibrosis by activating hypoxia-inducible factor-1α (HIF-1α), the specific roles of hypoxia and associated ERK phosphorylation in abnormal fibroblast activity during cutaneous scarring are unclear. Here, we investigated whether pathologic myofibroblast-like keloid fibroblast activity is promoted by hypoxia-induced epithelial–mesenchymal transition mediated by ERK activation. ERK phosphorylation was significantly increased in keloid tissue and fibroblasts. Human dermal fibroblasts cultured under hypoxia (1{\%} O2) expressed phosphorylated ERK and exhibited activation of p38 mitogen-activated protein kinase signaling. Hypoxic human dermal fibroblasts showed increased protein and mRNA levels of epithelial–mesenchymal transition markers. Furthermore, administration of an ERK inhibitor (SCH772984) reduced the hypoxia-induced elevation of collagen type I levels in human dermal fibroblasts. Therefore, ERK may be a promising therapeutic target in profibrogenic diseases.",
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Hypoxia-induced epithelial-to-mesenchymal transition mediates fibroblast abnormalities via EKR activation in cutaneous wound healing. / Kim, Jihee; Kim, Bomi; Kim, Soo Min; Yang, Chae Eun; Song, Seung Yong; Lee, Won Jai; Lee, JuHee.

In: International journal of molecular sciences, Vol. 20, No. 10, 2546, 02.05.2019.

Research output: Contribution to journalArticle

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AU - Kim, Jihee

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AU - Kim, Soo Min

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AU - Song, Seung Yong

AU - Lee, Won Jai

AU - Lee, JuHee

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AB - Previous studies described the involvement of extracellular signal-related kinase (ERK) in systemic fibrotic diseases, but the role of ERK in cutaneous scarring is unknown. Although hypoxia drives tissue fibrosis by activating hypoxia-inducible factor-1α (HIF-1α), the specific roles of hypoxia and associated ERK phosphorylation in abnormal fibroblast activity during cutaneous scarring are unclear. Here, we investigated whether pathologic myofibroblast-like keloid fibroblast activity is promoted by hypoxia-induced epithelial–mesenchymal transition mediated by ERK activation. ERK phosphorylation was significantly increased in keloid tissue and fibroblasts. Human dermal fibroblasts cultured under hypoxia (1% O2) expressed phosphorylated ERK and exhibited activation of p38 mitogen-activated protein kinase signaling. Hypoxic human dermal fibroblasts showed increased protein and mRNA levels of epithelial–mesenchymal transition markers. Furthermore, administration of an ERK inhibitor (SCH772984) reduced the hypoxia-induced elevation of collagen type I levels in human dermal fibroblasts. Therefore, ERK may be a promising therapeutic target in profibrogenic diseases.

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