Can we differentiate between airway and vascular smooth muscle?
1. Airway smooth muscle (ASM) has recently been termed the 'frustrated' cell of the lung given that contraction of ASM has no proven useful physiological function in adults and yet is indelibly associated with pathological conditions by virtue of its unwanted airflow-limiting actions in asthma. In contrast, pulmonary vascular smooth muscle contraction plays an essential role in the control of blood flow through the lung. 2. Little is known of the differences in phenotype between human ASM and pulmonary vascular smooth muscle (VSM) tissues, but differences in contractile protein and transcription factor expression and regulation of contractile protein promoter activity have been documented. Similarly, the embryological signals in mice required for differentiation of ASM versus pulmonary VSM are distinct. 3. Bronchoconstriction in asthma is currently treated with beta2-adrenoceptor agonists, which relax contracted ASM cells. An additional approach may be to use gene therapy to render ASM unable to contract (via disruption of their contractile apparatus organization). 4. Application of ASM-specific gene therapies would rely on minimal actions on other lung smooth muscle tissues, including pulmonary and bronchial vascular smooth muscle. The combination of mRNA analysis of laser-captured microdissected tissue with in situ immunohistochemical staining for protein should be very useful in terms of being able to characterize definitively the differences in mRNA and protein expression between the smooth muscle species of the lung. Any discovery of an ASM-selective target could provide a novel lead for ASM-directed anti-asthma therapy.
Fernandes
Darren J
DJ
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia. djfern@unimelb.edu.au
McConville
John F
JF
Stewart
Alastair G
AG
Kalinichenko
Vladimir
V
Solway
Julian
J
D000818:Animals; D006801:Humans; D009130:Muscle, Smooth / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D010641:Phenotype; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000254:growth & development; D012140:Respiratory Tract Diseases / Q000188:drug therapy / Q000503:physiopathology; D013234:Stem Cells / Q000502:physiology