Airway smooth muscle: A modulator of airway remodeling in asthma

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Presentation transcript:

Airway smooth muscle: A modulator of airway remodeling in asthma Aili L. Lazaar, MD, Reynold A. Panettieri, MD Journal of Allergy and Clinical Immunology Volume 116, Issue 3, Pages 488-495 (September 2005) DOI: 10.1016/j.jaci.2005.06.030 Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 1 Overview of ASM cell mitogenesis. In this simplified diagram of the intracellular pathways regulating ASM cell mitogenesis, Ras serves as a point of convergence for growth factor RTK and GPCR signaling. Ras activates ERK and PI3K, leading to activation of cyclins and cyclin-dependent kinases (CDKs). Activation of cyclin D1 ultimately leads to cell-cycle progression and cell proliferation. MEK, mitogen-activated protein kinase/ERK; NADPH, nicotinamide adenine dinucleotide phosphate; p70S6K, Ribosomal S6 kinase; ROS, reactive oxygen species. Journal of Allergy and Clinical Immunology 2005 116, 488-495DOI: (10.1016/j.jaci.2005.06.030) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 2 ASM-derived factors that promote airway remodeling, including matrix deposition, bronchial neovascularization, and leukocyte recruitment. Alterations in the ECM also affect ASM cell proliferation and migration. FN, Fibronectin; Coll, collagen; LN, laminin; HA, hyaluronan; CS, chondroitin sulfate; CTGF, connective tissue growth factor; TARC, thymus and activation-regulated chemokine; CAM, cell adhesion molecule. Journal of Allergy and Clinical Immunology 2005 116, 488-495DOI: (10.1016/j.jaci.2005.06.030) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 3 Cross-talk between ASM and inflammatory cells in asthma. T-cell adhesion through integrins and CD44 enhances ASM cell proliferation, agonist-induced calcium mobilization, and cytokine secretion. Mast cell–derived products enhance airway hyperresponsiveness (AHR) and modulate ASM proliferation. In turn, adhesion to ASM promotes T-cell and mast cell survival, as well as mast cell degranulation. The ? symbol highlights that the receptors mediating mast cell adhesion to ASM have not yet been defined. Journal of Allergy and Clinical Immunology 2005 116, 488-495DOI: (10.1016/j.jaci.2005.06.030) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions