MKP-1 Deficiency Exacerbates Skin Fibrosis in a Mouse Model of Scleroderma

Tutkimustuotos: ArtikkeliScientificvertaisarvioitu

5 Lataukset (Pure)

Abstrakti

Scleroderma is a chronic fibrotic disease, where proinflammatory and profibrotic events precede collagen accumulation. MKP-1 [mitogen-activated protein kinase (MAPK) phosphatase-1] downregulates inflammatory MAPK pathways suppressing inflammation. MKP-1 also supports Th1 polarization, which could shift Th1/Th2 balance away from profibrotic Th2 profile prevalent in scleroderma. In the present study, we investigated the potential protective role of MKP-1 in scleroderma. We utilized bleomycin-induced dermal fibrosis model as a well-characterized experimental model of scleroderma. Dermal fibrosis and collagen deposition as well as the expression of inflammatory and profibrotic mediators were analyzed in the skin samples. Bleomycin-induced dermal thickness and lipodystrophy were increased in MKP-1-deficient mice. MKP-1 deficiency enhanced collagen accumulation and increased expression of collagens, 1A1 and 3A1, in the dermis. Bleomycin-treated skin from MKP-1-deficient mice also showed enhanced expression of inflammatory and profibrotic factors IL-6, TGF-β1, fibronectin-1 and YKL-40, and chemokines MCP-1, MIP-1α and MIP-2, as compared to wild-type mice. The results show, for the first time, that MKP-1 protects from bleomycin-induced dermal fibrosis, suggesting that MKP-1 favorably modifies inflammation and fibrotic processes that drive the pathogenesis of scleroderma. Compounds enhancing the expression or activity of MKP-1 could thus prevent fibrotic processes in scleroderma and possess potential as a novel immunomodulative drug.

AlkuperäiskieliEnglanti
Artikkeli4668
JulkaisuInternational Journal of Molecular Sciences
Vuosikerta24
Numero5
DOI - pysyväislinkit
TilaJulkaistu - 2023
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Julkaisufoorumi-taso

  • Jufo-taso 1

!!ASJC Scopus subject areas

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

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