α-Defensins increase lung fibroblast proliferation and collagen synthesis via the β-catenin signaling pathway

Weihong Han, Wei Wang, Kamal A. Mohammed, Yunchao Su

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

α-defensins are released from granules of leukocytes and are implicated in inflammatory and fibrotic lung diseases. In the present study, the effects of α-defensins on the proliferation and collagen synthesis of lung fibroblasts were examined. We found that α-defensin-1 and α-defensin-2 induced dose-dependent increases in the incorporation of 5-bromo-2′-deoxy-uridine into newly synthesized DNA in two lines of human lung fibroblasts (HFL-1 and LL-86), suggesting that α-defensin-1 and α-defensin-2 stimulate the proliferation of lung fibroblasts. α-defensin-1 and α-defensin-2 also increased collagen-I mRNA (COL1A1) levels and protein contents of collagen-I and active/dephosphorylated β-catenin without changes in total β-catenin protein content in lung fibroblasts (HFL-1 and LL-86). Inhibition of the β-catenin signaling pathway using quercetin prevented increases in cell proliferation and the protein content of collagen-I and active/dephosphorylated β-catenin in lung fibroblasts, and in COL1A1 mRNA levels and collagen release into culture medium induced by α-defensin-1 and α-defensin-2. Knocking-down β-catenin using small interfering RNA technology also prevented α-defensin-induced increases in cell proliferation and the protein content of collagen-I and active/dephosphorylated β-catenin in lung fibroblasts, and in COL1A1 mRNA levels. Moreover, increases in the phosphorylation of glycogen synthase kinase 3β, accumulation/activation of β-catenin, and collagen synthesis induced by α-defensin-1 and α-defensin-2 were prevented by p38 mitogen-activated protein kinase inhibitor SB203580 and phosphoinositide 3-kinase inhibitor LY294002. These results indicate that α-defensin-1 and α-defensin-2 stimulate proliferation and collagen synthesis of lung fibroblasts. The β-catenin signaling pathway mediates α-defensin-induced increases in cell proliferation and collagen synthesis of lung fibroblasts. α-defensin-induced activation of β-catenin in lung fibroblasts might be caused by phosphorylation/inactivation of glycogen synthase kinase 3β as a result of the activation of the p38 mitogen-activated protein kinase and phosphoinositide 3-kinase/Akt pathways.

Original languageEnglish (US)
Pages (from-to)6603-6614
Number of pages12
JournalFEBS Journal
Volume276
Issue number22
DOIs
StatePublished - Nov 1 2009

Fingerprint

Defensins
Catenins
Fibroblasts
Collagen
Lung
Cell proliferation
Glycogen Synthase Kinase 3
Phosphorylation
1-Phosphatidylinositol 4-Kinase
Chemical activation
Cell Proliferation
p38 Mitogen-Activated Protein Kinases
Phosphatidylinositols
Messenger RNA
Phosphotransferases
MAP Kinase Kinase 3
Pulmonary diseases
Proteins
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one

Keywords

  • Collagen
  • Defensins
  • Fibroblasts
  • Proliferation
  • β-catenin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

α-Defensins increase lung fibroblast proliferation and collagen synthesis via the β-catenin signaling pathway. / Han, Weihong; Wang, Wei; Mohammed, Kamal A.; Su, Yunchao.

In: FEBS Journal, Vol. 276, No. 22, 01.11.2009, p. 6603-6614.

Research output: Contribution to journalArticle

Han, Weihong ; Wang, Wei ; Mohammed, Kamal A. ; Su, Yunchao. / α-Defensins increase lung fibroblast proliferation and collagen synthesis via the β-catenin signaling pathway. In: FEBS Journal. 2009 ; Vol. 276, No. 22. pp. 6603-6614.
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