The Coagulant Factor Xa Induces Protease-Activated Receptor-1 and Annexin A2-Dependent Airway Smooth Muscle Cytokine Production and Cell Proliferation
Research article published in American journal of respiratory cell and molecular biology (2016)
Abstract
During asthma exacerbation, plasma circulating coagulant factor X (FX) enters the inflamed airways and is activated (FXa). FXa may have an important role in asthma, being involved in thrombin activation and an agonist of protease-activated receptor-1 (PAR-1). Extracellular annexin A2 and integrins are also implicated in PAR-1 signaling. In this study, the potential role of PAR-1 in mediating the effects of FXa on human airway smooth muscle (ASM) cell cytokine production and proliferation was investigated. FXa (5-50 nM), but not FX, stimulated increases in ASM IL-6 production and cell number after 24- and 48-hour incubation, respectively (P < 0.05; n = 5). FXa (15 nM) also stimulated increases in the levels of mRNA for cytokines (IL-6), cell cycle-related protein (cyclin D1), and proremodeling proteins (FGF-2, PDGF-B, CTGF, SM22, and PAI-1) after 3-hour incubation (P < 0.05; n = 4). The actions of FXa were insensitive to inhibition by hirudin (1 U/ml), a selective thrombin inhibitor, but were attenuated by SCH79797 (100 nM), a PAR-1 antagonist, or Cpd 22 (1 μM), an inhibitor of integrin-linked kinase. The selective targeting of PAR-1, annexin A2, or β1-integrin by small interfering RNA and/or by functional blocking antibodies also attenuated FXa-evoked responses. In contrast, the targeting of annexin A2 did not inhibit thrombin-stimulated ASM function. In airway biopsies of patients with asthma, FXa and annexin A2 were detected in the ASM bundle by immunohistochemistry. These findings establish FXa as a potentially important asthma mediator, stimulating ASM function through actions requiring PAR-1 and annexin A2 and involving integrin coactivation.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
During asthma exacerbation, plasma circulating coagulant factor X (FX) enters the inflamed airways and is activated (FXa).
Por qué esto importa para la hirudoterapia
Este estudio investigó si el factor coagulante Xa estimula la producción de citoquinas y la proliferación de células de músculo liso de las vías respiratorias humanas (ASM) a través de PAR-1 y anexina A2, lo cual es relevante para el remodelado de las vías respiratorias en el asma. El resumen informa que los efectos del FXa fueron insensibles a la hirudina (1 U/ml), que el propio resumen identifica como un inhibidor selectivo de la trombina, pero fueron atenuados por un antagonista de PAR-1, un inhibidor de la quinasa ligada a integrinas, y la focalización de PAR-1, anexina A2 o β1-integrina. También se detectaron FXa y anexina A2 en haces de ASM de pacientes asmáticos mediante inmunohistoquímica en biopsias. Para ASH, la relevancia es limitada e indirecta: la hirudina aparece únicamente como reactivo de laboratorio para ayudar a distinguir los efectos mediados por FXa de los mediados por trombina, sin sanguijuelas, sin hirudoterapia y sin aplicación terapéutica de la hirudina.
Citación
The Coagulant Factor Xa Induces Protease-Activated Receptor-1 and Annexin A2-Dependent Airway Smooth Muscle Cytokine Production and Cell Proliferation
Schuliga M et al. · American journal of respiratory cell and molecular biology, 2016
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026