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Gene expression profile in the diaphragm following contractile inactivity during thoracic surgery

ABSTRACT: Recent work revealed the development of marked diaphragm muscle fiber weakness during two hours of thoracic surgery. This loss of muscle fiber function was not part of a generalized muscle weakness as function of the non-respiratory latissimus dorsi muscle was preserved. To disentangle the molecular processes that might underlie the development of diaphragm muscle fiber weakness during thoracic surgery we studied changes in the gene expression profile.

ORGANISM(S): Homo sapiens

PROVIDER: GSE30658 | GEO | 2013/07/03

SECONDARY ACCESSION(S): PRJNA144609

REPOSITORIES: GEO

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Gene expression profile in the diaphragm following contractile inactivity during thoracic surgery

Project description:Recent work revealed the development of marked diaphragm muscle fiber weakness during two hours of thoracic surgery. This loss of muscle fiber function was not part of a generalized muscle weakness as function of the non-respiratory latissimus dorsi muscle was preserved. To disentangle the molecular processes that might underlie the development of diaphragm muscle fiber weakness during thoracic surgery we studied changes in the gene expression profile. Analyzed were diaphragm samples at t0 vs t2 and latissimus dorsi at t0 vs t2. In total 8 Diaphragm samples and 6 latissimus dorsi samples were analyzed.

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Gene expression profile in the diaphragm following contractile inactivity during thoracic surgery.

Project description:Introduction. Recent work revealed the development of marked muscle fiber weakness in the diaphragm, but not in the non-respiratory latissimus dorsi, during thoracic surgery. To disentangle the molecular processes that underlie the development of diaphragm muscle fiber weakness during thoracic surgery, we studied changes in the gene expression profile. Methods. Serial biopsies from the diaphragm and the latissimus dorsi muscle were obtained from four patients during thoracotomy for resection of a tumor in the right lung. Biopsies were taken as soon as the diaphragm had been exposed (t0) and again after two hours (t2). Gobal differences in gene expression in diaphragm biopsies were assessed by microarray analysis. Results. 346 differentially expressed gene transcripts were found in the diaphragm at t2 vs. t0. Pathway analysis revealed that genes associated with inflammation (83 genes; p<0.0001) and cell death (118 genes, p<0.0001) pathways were significantly overexpressed at t2. Of the 346 differentially expressed genes in the diaphragm at t2, 258 were also differential in the latissimus dorsi muscle, with the direction of change being identical for all differentially expressed genes. In addition, latissimus dorsi showed exclusive upregula-ton of negative regulators of cell death. Conclusions. Two hours of thoracic surgery result in rapid and profound changes in expression of inflammatory response and apoptotic genes in the diaphragm. The apoptotic response was stronger in the diaphragm than in the latissiums dorsi. These findings suggest that the development of selective diaphragm muscle fiber weakness in these patients might be related to an exaggerated apoptotic response.

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Project description:Type 2 diabetes differs from type 1 diabetes in its pathogenesis. Type 1 diabetic diaphragm has altered gene expression which includes lipid and carbohydrate metabolism, ubiquitination and oxidoreductase activity. The objectives of the present study were to assess respiratory muscle gene expression changes in type 2 diabetes and to determine whether they are greater for the diaphragm than an upper airway muscle. Diaphragm and sternohyoid muscle from Zucker diabetic fatty (ZDF) rats were analyzed with Affymetrix gene expression arrays. The two muscles had 97 and 102 genes, respectively, with at least ±1.5-fold significantly changed expression with diabetes, and these were assigned to gene ontology groups based on over-representation analysis. Several significantly changed groups were common to both muscles, including lipid metabolism, carbohydrate metabolism, muscle contraction, ion transport and collagen, although the number of genes and the specific genes involved differed considerably for the two muscles. In both muscles there was a shift in metabolism gene expression from carbohydrate metabolism toward lipid metabolism, but the shift was greater and involved more genes in diabetic diaphragm than diabetic sternohyoid muscle. Groups present in only diaphragm were blood circulation and oxidoreductase activity. Groups present in only sternohyoid were immune & inflammation and response to stress & wounding, with complement genes being a prominent component. In conclusion, type 2 diabetes-induced gene expression changes in respiratory muscles has both similarities and differences relative to previous data on type 1 diabetes gene expression. Furthermore, the diabetic alterations in gene expression differ between diaphragm and sternohyoid.

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Zucker Diabetic Fatty (ZDF) Rat Study - Diaphragm vs. Sternohyoid

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