ArticleLaboratory investigation; a journal of technical methods and pathology2014
LL-37 secreted by epithelium promotes fibroblast collagen production: a potential mechanism of small airway remodeling in chronic obstructive pulmonary disease.
Article in Laboratory investigation; a journal of technical methods and pathology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 49 citations in OpenAlex.
- Expression of Matrix Metalloproteinase-2, Matrix Metalloproteinase-9, Tissue Inhibitor of Metalloproteinase-1, and Changes in Alveolar Septa in Patients with Chronic Obstructive Pulmonary Disease.Medical science monitor : international medical journal of experimental and clinical research · 2020Trial
- The role of FGF-2 in smoke-induced emphysema and the therapeutic potential of recombinant FGF-2 in patients with COPD.Experimental & molecular medicine · 2018Trial
- Lung antimicrobial proteins and peptides: from host defense to therapeutic strategies.Physiological reviews · 2024Review
- LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases.Biomolecules · 2024Review
- Epithelial-Mesenchymal Transition Mechanisms in Chronic Airway Diseases: A Common Process to Target?International journal of molecular sciences · 2023Review
- Antimicrobial Peptides: Challenging Journey to the Pharmaceutical, Biomedical, and Cosmeceutical Use.International journal of molecular sciences · 2023Review
- Effects of hypoxia on bronchial and alveolar epithelial cells linked to pathogenesis in chronic lung disorders.Frontiers in physiology · 2023Article
- A Scoping Analysis of Cathelicidin in Response to Organic Dust Exposure and Related Chronic Lung Illnesses.International journal of molecular sciences · 2022Article
- Article
- HB-EGF-induced IL-8 secretion from airway epithelium leads to lung fibroblast proliferation and migration.BMC pulmonary medicine · 2021Article
- Family with sequence similarity 13 member A mediates TGF-β1-induced EMT in small airway epithelium of patients with chronic obstructive pulmonary disease.Respiratory research · 2021Article
- Responsiveness of human bronchial fibroblasts and epithelial cells from asthmatic and non-asthmatic donors to the transforming growth factor-βBMC molecular and cell biology · 2021Article
- Distinct contributions of cathelin-related antimicrobial peptide (CRAMP) derived from epithelial cells and macrophages to colon mucosal homeostasis.The Journal of pathology · 2021Article
- Cathelicidin induces epithelial-mesenchymal transition to promote airway remodeling in smoking-related chronic obstructive pulmonary disease.Annals of translational medicine · 2021Article
- Epithelial Barrier Dysfunction in Chronic Respiratory Diseases.Frontiers in physiology · 2021Review
- Formyl peptide receptors in the mucosal immune system.Experimental & molecular medicine · 2020Review
- Vascular endothelial growth factor enhances profibrotic activities through modulation of calcium homeostasis in human atrial fibroblasts.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Review
- Differential Expression of Antimicrobial Peptides in Streptococcus pneumoniae Keratitis and STAT3-Dependent Expression of LL-37 by Streptococcus pneumoniae in Human Corneal Epithelial Cells.Pathogens (Basel, Switzerland) · 2019Article
- Cathelicidin LL-37 restoring glucocorticoid function in smoking and lipopolysaccharide-induced airway inflammation in rats.Chinese medical journal · 2019Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Emerging evidence suggests that the process of small airway remodeling is mediated by profibrotic growth factors produced by epithelium, which are capable of activating the underlying mesenchymal cells with excessive collagen production. It has been demonstrated that human cathelicidin antimicrobial protein LL-37 is highly expressed in small airway epithelium from COPD patients. However, it is unknown whether the increased levels of LL-37 in epithelium are involved in the pathogenesis of small airway remodeling in COPD. In this study, we examined the expression of LL-37 in small airways from smokers with COPD and controls (non-smokers and smokers without COPD) by immunohistochemistry, and then the association between LL-37 expression in epithelium and the structural changes of small airway remodeling was analyzed. In vitro, the effect of CSE-induced epithelial secretion of LL-37 on collagen production in human lung fibroblasts (HFL-1 cell line) was studied in a co-culture system. Finally, the signaling pathways involved in the effect of LL-37 on fibroblast collagen production were evaluated. The results showed that LL-37 immunoreactivity in airway epithelium was significantly elevated in smokers with COPD compared with controls. In addition, the magnitude of LL-37 expression in epithelium was positively correlated with airway wall thickness and collagen deposition. In vitro, CSE-induced epithelial secretion of LL-37 promoted fibroblast collagen production. Finally, we showed that formyl peptide receptor-like 1 (FPRL1)-dependent extracellular signal-regulated kinase (ERK) signaling pathway was essential for LL-37-induced collagen production in HFL-1 cells. These results suggest that after cigarette smoke exposure, the increased levels of LL-37 in airway epithelium could stimulate collagen production in the underlying lung fibroblasts and may contribute to small airway remodeling in COPD.
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