The Role of Airway Smooth Muscle in the Pathogenesis of Asthma.
- Author:
Jung Yeon SHIM
1
Author Information
1. Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
- Publication Type:Review
- Keywords:
Airway smooth muscle;
Proliferation;
Extracellular matrix;
Steroid;
Cytokine
- MeSH:
Apoptosis;
Asthma*;
Cell Adhesion;
Cell Movement;
Cell Proliferation;
Chemokines;
Cytokines;
Extracellular Matrix;
Extracellular Matrix Proteins;
Hyperplasia;
Hypertrophy;
Intercellular Signaling Peptides and Proteins;
Mitogens;
Muscle, Smooth*;
p21-Activated Kinases;
Phosphotransferases;
Protein Kinases;
Receptors, Glucocorticoid;
Signal Transduction
- From:Pediatric Allergy and Respiratory Disease
2005;15(3):227-234
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Airway smooth muscle (ASM) hypertrophy and hyperplasia, important pathological features in chronic severe asthma, contribute to irreversible airflow obstruction. ASM, which had been known to be a structural cell, may act as an immunomodulatory cell by providing pro- inflammatory cytokines and chemokines, polypeptide growth factors, extracellular matrix proteins, cell adhesion receptors and co-stimulatory molecules. ASM can promote the formation of the interstitial extracellular matrix, and potentially contribute to the alterations within the extracellular matrix in asthma. In addition, extracellular matrix components can alter the proliferative, survival, and cytoskeletal synthetic function of ASM cells through integrin- directed signaling. Increased ASM mass is one of the most important features of the airway wall remodeling process in asthma. Despite considerable research effort, the precise cellular mechanisms that modulate ASM growth remain unknown. Three different mechanisms may contribute to the increased ASM mass: cell proliferation or hypertrophy, increased migration and decreased rate of apoptosis. The major signaling pathways of cell proliferation activated by ASM mitogens are those dependent on extracellular signal-regulated kinase and phosphoinositide 3'-kinase. The key signaling mechanisms of cell migration have been identified as the p38 mitogen-activated protein kinase and the p21-activated kinase 1 pathways. ASM cells contain beta2-adrenergic receptors and glucocorticoid receptors. They may represent a key target for beta2-adrenergic receptor agonist/corticosteroid interactions which may have antiproliferative activity against a broad spectrum of mitogens. But corticosteroid itself, with or without beta2-adrenergic receptor agonist, cannot inhibit or reduce ASM cell proliferation completely. Future therapy should focus on blocking intracellular signal pathway which regulates proliferation.
