Gene expression microarrays and respiratory muscles.
The routine measurement of the expression of tens of thousands of gene transcripts, simultaneously, is a defining advance of the last decade which has been made possible by microarray technology. Using this very powerful approach, a pattern has emerged from a number of studies that suggest a molecular niche for the diaphragm which is quite different from that occupied by limb muscle. All indications are that this is true not only in regard to differential gene transcription patterns in healthy muscles but also in the changes in transcription occurring in association with different diseases. Furthermore, respiratory muscle mounts a rich gene expression response to a number of disturbances, be they primary genetic defects (e.g. various types of muscular dystrophies) or non-genetic perturbations (e.g. controlled mechanical ventilation). Large numbers of genes undergo altered levels of transcription, ranging from tens to hundreds (typical) to thousands. These genes are involved in diverse cellular processes, such as contraction, intermediate metabolism, oxidative stress, apoptosis and cellular adhesion. Functional groups of genes identified as having changed expression differ in many respects from one disease to another. Previously identified pathways of muscle injury and repair are often perturbed to greater extents than previously anticipated, and processes not previously suspected of having important roles in the pathophysiology of specific disorders have been identified. Elucidation of these under-appreciated molecular events may lead to novel therapeutic interventions based on disrupting the downstream adverse consequences of the primary event or facilitating events which ameliorate the injury and/or promote muscle healing.
van Lunteren
Erik
E
Division of Pulmonary, Critical Care and Sleep Medicine, Cleveland VA Medical Center and Case Western Reserve University, Cleveland, OH 44106, United States. exv4@cwru.edu
Leahy
Patrick
P
D000818:Animals; D003964:Diaphragm / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D018482:Muscle, Skeletal / Q000502:physiology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012121:Respiration, Artificial; D012132:Respiratory Muscles / Q000502:physiology; D012143:Respiratory Physiological Phenomena