ArticleThe FEBS journal2009
Alpha-defensins increase lung fibroblast proliferation and collagen synthesis via the beta-catenin signaling pathway.
Article in The FEBS journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 28 citations in OpenAlex.
- Role of innate host defense proteins in oral cancerogenesis.Periodontology 2000 · 2024Review
- Regulation of dermal fibroblasts by human neutrophil peptides.Scientific reports · 2023Article
- Integrated analysis of microRNA and mRNA expression profiles in splenomegaly induced by non-cirrhotic portal hypertension in rats.Scientific reports · 2018Article
- Plasma levels of alarmin HNPs 1-3 associate with lung dysfunction after cardiac surgery in children.BMC pulmonary medicine · 2017Article
- Quercetin Inhibits Fibroblast Activation and Kidney Fibrosis Involving the Suppression of Mammalian Target of Rapamycin and β-catenin Signaling.Scientific reports · 2016Article
- Humanized anti-hepatocyte growth factor (HGF) antibody suppresses innate irinotecan (CPT-11) resistance induced by fibroblast-derived HGF.Oncotarget · 2015Article
- Nonenzymatic conversion of ADP-ribosylated arginines to ornithine alters the biological activities of human neutrophil peptide-1.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Quercetin attenuates warfarin-induced vascular calcification in vitro independently from matrix Gla protein.The Journal of biological chemistry · 2013Article
- Transglutaminase inhibitors attenuate vascular calcification in a preclinical model.Arteriosclerosis, thrombosis, and vascular biology · 2013Article
- The peripheral blood transcriptome identifies the presence and extent of disease in idiopathic pulmonary fibrosis.PloS one · 2012Article
- High fidelity processing and activation of the human α-defensin HNP1 precursor by neutrophil elastase and proteinase 3.PloS one · 2012Article
- A novel glycerophosphodiester phosphodiesterase, GDE5, controls skeletal muscle development via a non-enzymatic mechanism.The Journal of biological chemistry · 2010Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Alpha-defensins are released from granules of leukocytes and are implicated in inflammatory and fibrotic lung diseases. In the present study, the effects of alpha-defensins on the proliferation and collagen synthesis of lung fibroblasts were examined. We found that alpha-defensin-1 and alpha-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 alpha-defensin-1 and alpha-defensin-2 stimulate the proliferation of lung fibroblasts. alpha-defensin-1 and alpha-defensin-2 also increased collagen-I mRNA (COL1A1) levels and protein contents of collagen-I and active/dephosphorylated beta-catenin without changes in total beta-catenin protein content in lung fibroblasts (HFL-1 and LL-86). Inhibition of the beta-catenin signaling pathway using quercetin prevented increases in cell proliferation and the protein content of collagen-I and active/dephosphorylated beta-catenin in lung fibroblasts, and in COL1A1 mRNA levels and collagen release into culture medium induced by alpha-defensin-1 and alpha-defensin-2. Knocking-down beta-catenin using small interfering RNA technology also prevented alpha-defensin-induced increases in cell proliferation and the protein content of collagen-I and active/dephosphorylated beta-catenin in lung fibroblasts, and in COL1A1 mRNA levels. Moreover, increases in the phosphorylation of glycogen synthase kinase 3beta, accumulation/activation of beta-catenin, and collagen synthesis induced by alpha-defensin-1 and alpha-defensin-2 were prevented by p38 mitogen-activated protein kinase inhibitor SB203580 and phosphoinositide 3-kinase inhibitor LY294002. These results indicate that alpha-defensin-1 and alpha-defensin-2 stimulate proliferation and collagen synthesis of lung fibroblasts. The beta-catenin signaling pathway mediates alpha-defensin-induced increases in cell proliferation and collagen synthesis of lung fibroblasts. alpha-defensin-induced activation of beta-catenin in lung fibroblasts might be caused by phosphorylation/inactivation of glycogen synthase kinase 3beta as a result of the activation of the p38 mitogen-activated protein kinase and phosphoinositide 3-kinase/Akt pathways.
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