Gene Expression Profiling in Vastus Lateralis Muscle During an Acute Exacerbation of COPD
Open accessAbstract
BACKGROUND/AIMS: The molecular mechanisms leading to loss in muscle force during an acute exacerbation in COPD patients are unknown. A cross-sectional study was designed to compare the gene expression profile of the vastus lateralis muscle in patients with an acute COPD exacerbation and in stable COPD patients. METHODS: Muscle biopsies were taken in 9 COPD patients with an exacerbation on day 4 of hospitalization and in 15 stable COPD patients. Micro-array was performed on an UniSet Human 20K Bioarray. RESULTS: Gene Ontology and Gene Set Enrichment Analysis of the microarray data revealed enrichment of 1) the ubiquitin-dependent protein catabolism, the induction of apoptosis and anti-apoptosis and the response to reactive oxygen species in the upregulated transcripts, and 2) the aspartate catabolism and the mitochondrial respiratory chain in the downregulated transcripts. Real Time PCR data confirmed 1) increased expression of MuRF1 and MAFbx, markers of the ubiquitin dependent catabolism pathway, and 2) decreased expression levels of COX6C, a marker of mitochondrial respiration. CONCLUSIONS: The present study suggests that multiple pathways leading to muscle atrophy and mitochondrial dysfunction are altered in the muscle during an acute exacerbation. Strategies limiting the loss of muscle function during an acute exacerbation need to be developed.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
During COPD exacerbations, mitochondrial respiration appears further decreased, with decreased aspartate catabolism and COX6C activity in quadriceps.
“During exacerbations, mitochondrial respiration seems to be further decreased, as confirmed by a study investigating the transcriptomic profile of quadriceps biopsies between exacerbating COPD patients and stable COPD controls, and evidencing a decreased aspartate catabolism as well as COX6C activity [104].”
From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [104]
The Discussion reports downregulated aspartate catabolism and mitochondrial respiratory-chain pathways in vastus lateralis muscle during exacerbation. The Real-time PCR data section reports lower COX6C mRNA in exacerbating patients than in stable COPD patients, but it does not establish decreased COX6C activity; that part of the claim overstates the measurement. (LLM, conf=0.88)
Experimental — accuracy not yet measuredDuring exacerbations, the ubiquitin-proteasome pathway seems further enhanced in the quadriceps with upregulation of MuRF-1 and Atrogin-1 expression.
“During exacerbations, this pathway seems to be further enhanced in the quadriceps with the upregulation of MuRF-1 and Atrogin-1 expression [104].”
From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [104]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 35 · Cited by 79
Research works printed but not linked: 32
- Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, Fukuchi Y, Jenkins C, Rodriguez-Roisin R, van Weel C, Zielinski J: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2007;176:532-555.
- Agusti AG, Noguera A, Sauleda J, Sala E, Pons J, Busquets X: Systemic effects of chronic obstructive pulmonary disease. Eur Respir J 2003;21:347-360.
- Pitta F, Troosters T, Spruit MA, Probst VS, Decramer M, Gosselink R: Characteristics of physical activities in daily life in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005;171:972-977.
- Pitta F, Troosters T, Spruit MA, Decramer M, Gosselink R: Activity monitoring for assessment of physical activities in daily life in patients with chronic obstructive pulmonary disease. Arch Phys Med Rehabil 2005;86:1979- 1985.
- Decramer M, Lacquet LM, Fagard R, Rogiers P: Corticosteroids contribute to muscle weakness in chronic airflow obstruction. Am J Respir Crit Care Med 1994;150:11-16.
- Debigare R, Cote CH, Maltais F: Peripheral muscle wasting in chronic obstructive pulmonary disease. Clinical relevance and mechanisms. Am J Respir Crit Care Med 2001;164:1712-1717.
- Couillard A, Maltais F, Saey D, Debigare R, Michaud A, Koechlin C, LeBlanc P, Prefaut C: Exercise-induced quadriceps oxidative stress and peripheral muscle dysfunction in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2003;167:1664- 1669.
- Debigare R, Maltais F, Cote CH, Michaud A, Caron MA, Mofarrahi M, LeBlanc P, Hussain SN: Profiling of mRNA expression in quadriceps of patients with COPD and muscle wasting. COPD 2008;5:75-84.
- Radom-Aizik S, Kaminski N, Hayek S, Halkin H, Cooper DM, Ben-Dov I: Effects of exercise training on quadriceps muscle gene expression in chronic obstructive pulmonary disease. J Appl Physiol 2007;102:1976-1984.
- Donaldson GC, Seemungal TA, Bhowmik A, Wedzicha JA: Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 2002;57:847-852.
- Seemungal TA, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, Wedzicha JA: Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157:1418-1422.
- Soler-Cataluna JJ, Martinez-Garcia MA, Roman SP, Salcedo E, Navarro M, Ochando R: Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax 2005;60:925-931.
- Spruit MA, Gosselink R, Troosters T, Kasran A, Gayan-Ramirez G, Bogaerts P, Bouillon R, Decramer M: Muscle force during an acute exacerbation in hospitalised patients with COPD and its relationship with CXCL8 and IGF-I. Thorax 2003;58:752-756.
- Crul T, Spruit MA, Gayan-Ramirez G, Quarck R, Gosselink R, Troosters T, Pitta F, Decramer M: Markers of inflammation and disuse in vastus lateralis of chronic obstructive pulmonary disease patients. Eur J Clin Invest 2007;37:897-904.
- Backes C, Keller A, Kuentzer J, Kneissl B, Comtesse N, Elnakady YA, Muller R, Meese E, Lenhof HP: GeneTrail- advanced gene set enrichment analysis. Nucleic Acids Res 2007;35:W186-W192.
- Dennis G, Jr., Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA: DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol 2003;4:3.
- Huang da W, Sherman BT, Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009;4:44-57.
- Doucet M, Russell AP, Leger B, Debigare R, Joanisse DR, Caron MA, LeBlanc P, Maltais F: Muscle Atrophy and Hypertrophy Signalling in Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med 2007;176:261-269.
- Rutten EP, Franssen FM, Engelen MP, Wouters EF, Deutz NE, Schols AM: Greater whole-body myofibrillar protein breakdown in cachectic patients with chronic obstructive pulmonary disease. Am J Clin Nutr 2006;83:829-834.
- Barreiro E, de la Puente B, Minguella J, Corominas JM, Serrano S, Hussain SN, Gea J: Oxidative stress and respiratory muscle dysfunction in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005;171:1116- 1124.
- Barreiro E, Schols AM, Polkey MI, Galdiz JB, Gosker HR, Swallow EB, Coronell C, Gea J: Cytokine profile in quadriceps muscles of patients with severe chronic obstructive pulmonary disease. Thorax 2008;63:100-107.
- Puente-Maestu L, Perez-Parra J, Godoy R, Moreno N, Tejedor A, Gonzalez- Aragoneses F, Bravo JL, Villar F, Camano S, Agusti A: Abnormal mitochondrial function in locomotor and respiratory muscles of COPD patients. Eur Respir J 2009;33:1045-1052.
- Couillard A, Prefaut C: From muscle disuse to myopathy in COPD: potential contribution of oxidative stress. Eur Respir J 2005;26:703-719.
- Allen DL, Linderman JK, Roy RR, Bigbee AJ, Grindeland RE, Mukku V, Edgerton VR: Apoptosis: a mechanism contributing to remodeling of skeletal muscle in response to hindlimb unweighting. Am J Physiol 1997;273:C579-C587.
- Allen DL, Roy RR, Edgerton VR: Myonuclear domains in muscle adaptation and disease. Muscle Nerve 1999;22:1350-1360.
- Vescovo G, Volterrani M, Zennaro R, Sandri M, Ceconi C, Lorusso R, Ferrari R, Ambrosio GB, Dalla LL: Apoptosis in the skeletal muscle of patients with heart failure: investigation of clinical and biochemical changes. Heart 2000;84:431-437.
- Sauleda J, Garcia-Palmer F, Wiesner RJ, Tarraga S, Harting I, Tomas P, Gomez C, Saus C, Palou A, Agusti AG: Cytochrome oxidase activity and mitochondrial gene expression in skeletal muscle of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157:1413-1417.
- 3 Lewis MI: Apoptosis as a potential mechanism of muscle cachexia in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:434-436.
- Rabinovich RA, Bastos R, Ardite E, Llinas L, Orozco-Levi M, Gea J, Vilaro J, Barbera JA, Rodriguez-Roisin R, Fernandez- Checa JC, Roca J: Mitochondrial dysfunction in COPD patients with low body mass index. Eur Respir J 2007;29:643-650.
- Boss O, Samec S, Paoloni-Giacobino A, Rossier C, Dulloo A, Seydoux J, Muzzin P, Giacobino JP: Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression. FEBS Lett 1997;408:39-42.
- Vidal-Puig AJ, Grujic D, Zhang CY, Hagen T, Boss O, Ido Y, Szczepanik A, Wade J, Mootha V, Cortright R, Muoio DM, Lowell BB: Energy metabolism in uncoupling protein 3 gene knockout mice. J Biol Chem 2000;275:16258- 16266.
- Crul/Testelmans/Spruit/Troosters/Gosselink/Geeraerts/Decramer/ Gayan-Ramirez Cell Physiol Biochem 2010;25:491-500
- Authors
- Crul, T., Testelmans, D., Spruit, M., Troosters, T., Gosselink, R., Geeraerts, I., Decramer, M., & Gayan-Ramirez, G.
- Affiliations
- KU Leuven (BE)
- Venue
- Cellular Physiology and Biochemistry
- Publisher
- S. Karger AG
- Published
- 2010
- Volume
- 25
- Issue
- 4-5
- Pages
- 491-500
- ISSN
- 1015-8987 (ISSN-L)
- 1421-9778
- OpenAlex
- W2042660834
- Cited by
- 79
- References
- 35
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 3 · 2020: 6 · 2019: 2 · 2018: 3 · 2017: 5 · 2016: 6 · 2015: 6 · 2014: 11 · 2013: 7 · 2012: 7
- FWCI
- 3.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cellular Physiology and Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion, other-oa)
- Funders
- AstraZeneca
- Fonds Wetenschappelijk Onderzoek
- Vlaamse regering
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Keywords
- COPD exacerbations, vastus lateralis, skeletal muscle gene expression, muscle atrophy, MuRF1, atrogin-1, apoptosis, reactive oxygen species, mitochondrial dysfunction, muscle force loss
- MeSH terms
- Tripartite Motif Proteins, Acute Disease, Aged, Cross-Sectional Studies, Electron Transport Complex IV, Humans, Male, Middle Aged, Muscle Proteins, Biomarkers, Gene Expression Profiling, Pulmonary Disease, Chronic Obstructive, Ubiquitin-Protein Ligases, SKP Cullin F-Box Protein Ligases, Microarray Analysis, Quadriceps Muscle
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
