ArticlePhysiological reports2015
Activation of protease-activated receptors (PARs)-1 and -2 promotes alpha-smooth muscle actin expression and release of cytokines from human lung fibroblasts.
Article in Physiological reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 22 citations in OpenAlex.
- Protease-Activated Receptor-2 as a Proteolytic Rheostat in Colorectal and Pancreatic Cancer: From Mechanism to Biomarker-Guided Therapy.International journal of molecular sciences · 2026Review
- Systemic sclerosis, main culprits and involved signaling pathways.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Thrombin-Induced COX-2 Expression and PGEInternational journal of molecular sciences · 2023Article
- Japanese cedar pollen upregulates the effector functions of eosinophils.Asia Pacific allergy · 2021Article
- Soluble Dipeptidyl Peptidase-4 Induces Fibroblast Activation Through Proteinase-Activated Receptor-2.Frontiers in pharmacology · 2020Article
- Regulation of IL-17A and implications for TGF-β1 comodulation of airway smooth muscle remodeling in severe asthma.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- The co-expression of MMP-9 and Tenascin-C is significantly associated with the progression and prognosis of pancreatic cancer.Diagnostic pathology · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Previous studies have shown that protease-activated receptors (PARs) play an important role in various physiological processes. In the present investigation, we determined the expression of PARs on human lung fibroblasts (HLF-1) and whether they were involved in cellular differentiation and pro-inflammatory cytokine and prostaglandin (PGE2) secretion. PAR-1, PAR-2, PAR-3, and PAR-4 were detected in fibroblasts using RT-PCR, immunocytochemistry, and flow cytometry. Increased expression of PAR-4, but not other PARs, was observed in fibroblasts stimulated with phorbol myristate acetate. The archetypical activators of PARs, namely, thrombin and trypsin, as well as PAR-1 and PAR-2 agonist peptides, stimulated transient increases in intracellular Ca(2+), and promoted increased α-smooth muscle actin expression. The proteolytic and peptidic PAR activators also stimulated the release of IL-6 and IL-8, as well as PGE2, with a rank order of potency of PAR-1 > PAR-2. The combined stimulation of PAR-1 and PAR-2 resulted in an additive release of both IL-6 and IL-8. In contrast, PAR-3 and PAR-4 agonist peptides, as well as all the PAR control peptides examined, were inactive. These results suggest an important role for PARs associated with fibroblasts in the modulation of inflammation and remodeling in the airway.
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