Factors controlling smooth muscle proliferation and airway remodelling.
It is clear that airway smooth muscle plays an important role in the hyperresponsiveness and remodelling that occur in the asthmatic airway. This is by virtue of its roles as a contractile cell, a cell that undergoes proliferation as part of the inflammatory response, a cell that actively participates in the inflammatory response via the production of cytokines and chemokines, and perhaps as a cell that undergoes migration. Now that airway smooth muscle cells cultured from asthmatic patients have been studied in vitro, it is apparent that there is an abnormality in the growth of these cells such that they grow more rapidly than cells derived from nonasthmatic patients. This raises the possibility of identifying the exact point(s) in the signal transduction pathways at which this abnormality occurs. To do this it is necessary to define precisely the mitogenic pathways that lead to proliferation in the airway smooth muscle cell, and this information is accumulating rapidly. The possibility is raised for new therapeutic targets that are aimed specifically at the airway smooth muscle, leading to an effective method for reversing or preventing the airway remodelling that accompanies chronic severe asthma.
Black
Judith L
JL
Department of Pharmacology, University of Sydney, New South Wales, Australia 2006. judblack@pharmacol.usyd.edu.au
Johnson
Peter R A
PR
D000402:Airway Obstruction / Q000150:complications / Q000378:metabolism; D001249:Asthma / Q000473:pathology*; D001980:Bronchi / Q000473:pathology*; D002465:Cell Movement; D002478:Cells, Cultured / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008246:Lysophospholipids; D009130:Muscle, Smooth / Q000276:immunology / Q000473:pathology*; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000378:metabolism / Q000627:therapeutic use; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism
D008246:Lysophospholipids; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; C060506:sphingosine 1-phosphate; D013110:Sphingosine