PubMed:17380205 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/17380205","sourcedb":"PubMed","sourceid":"17380205","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/17380205","text":"Interplay of IKK/NF-kappaB signaling in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy.\nDuchenne muscular dystrophy (DMD) is a lethal X-linked disorder associated with dystrophin deficiency that results in chronic inflammation and severe skeletal muscle degeneration. In DMD mouse models and patients, we find that IkappaB kinase/NF-kappaB (IKK/NF-kappaB) signaling is persistently elevated in immune cells and regenerative muscle fibers. Ablation of 1 allele of the p65 subunit of NF-kappaB was sufficient to improve pathology in mdx mice, a model of DMD. In addition, conditional deletion of IKKbeta in mdx mice elucidated that NF-kappaB functions in activated macrophages to promote inflammation and muscle necrosis and in skeletal muscle fibers to limit regeneration through the inhibition of muscle progenitor cells. Furthermore, specific pharmacological inhibition of IKK resulted in improved pathology and muscle function in mdx mice. Collectively, these results underscore the critical role of NF-kappaB in the progression of muscular dystrophy and suggest the IKK/NF-kappaB signaling pathway as a potential therapeutic target for DMD.","tracks":[{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":136,"end":154},"obj":"HP_0003560"},{"id":"T2","span":{"begin":173,"end":181},"obj":"HP_0001417"},{"id":"T3","span":{"begin":1073,"end":1091},"obj":"HP_0003560"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubmedHPO"},{"subj":"T2","pred":"source","obj":"PubmedHPO"},{"subj":"T3","pred":"source","obj":"PubmedHPO"}]},{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":207,"end":217},"obj":"gene:1756"},{"id":"T1","span":{"begin":286,"end":305},"obj":"disease:C0234958"},{"id":"T2","span":{"begin":207,"end":217},"obj":"gene:1756"},{"id":"T3","span":{"begin":127,"end":159},"obj":"disease:C0013264"},{"id":"T4","span":{"begin":506,"end":509},"obj":"gene:65125"},{"id":"T5","span":{"begin":591,"end":594},"obj":"disease:C0026850"},{"id":"T6","span":{"begin":506,"end":509},"obj":"gene:5970"},{"id":"T7","span":{"begin":591,"end":594},"obj":"disease:C0026850"},{"id":"T8","span":{"begin":506,"end":509},"obj":"gene:6857"},{"id":"T9","span":{"begin":591,"end":594},"obj":"disease:C0026850"},{"id":"T10","span":{"begin":506,"end":509},"obj":"gene:64689"},{"id":"T11","span":{"begin":591,"end":594},"obj":"disease:C0026850"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"},{"id":"R3","pred":"associated_with","subj":"T4","obj":"T5"},{"id":"R4","pred":"associated_with","subj":"T6","obj":"T7"},{"id":"R5","pred":"associated_with","subj":"T8","obj":"T9"},{"id":"R6","pred":"associated_with","subj":"T10","obj":"T11"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"},{"subj":"T4","pred":"source","obj":"DisGeNET"},{"subj":"T5","pred":"source","obj":"DisGeNET"},{"subj":"T6","pred":"source","obj":"DisGeNET"},{"subj":"T7","pred":"source","obj":"DisGeNET"},{"subj":"T8","pred":"source","obj":"DisGeNET"},{"subj":"T9","pred":"source","obj":"DisGeNET"},{"subj":"T10","pred":"source","obj":"DisGeNET"},{"subj":"T11","pred":"source","obj":"DisGeNET"}]},{"project":"sentences","denotations":[{"id":"TextSentencer_T1","span":{"begin":0,"end":126},"obj":"Sentence"},{"id":"TextSentencer_T2","span":{"begin":127,"end":306},"obj":"Sentence"},{"id":"TextSentencer_T3","span":{"begin":307,"end":477},"obj":"Sentence"},{"id":"TextSentencer_T4","span":{"begin":478,"end":595},"obj":"Sentence"},{"id":"TextSentencer_T5","span":{"begin":596,"end":860},"obj":"Sentence"},{"id":"TextSentencer_T6","span":{"begin":861,"end":980},"obj":"Sentence"},{"id":"TextSentencer_T7","span":{"begin":981,"end":1182},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":126},"obj":"Sentence"},{"id":"T2","span":{"begin":127,"end":306},"obj":"Sentence"},{"id":"T3","span":{"begin":307,"end":477},"obj":"Sentence"},{"id":"T4","span":{"begin":478,"end":595},"obj":"Sentence"},{"id":"T5","span":{"begin":596,"end":860},"obj":"Sentence"},{"id":"T6","span":{"begin":861,"end":980},"obj":"Sentence"},{"id":"T7","span":{"begin":981,"end":1182},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"TextSentencer_T1","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T2","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T3","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T4","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T5","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T6","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T7","pred":"source","obj":"sentences"},{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"},{"subj":"T7","pred":"source","obj":"sentences"}]},{"project":"DisGeNet-2017-sample","denotations":[{"id":"T1537","span":{"begin":506,"end":509},"obj":"gene:64689"},{"id":"T1538","span":{"begin":591,"end":594},"obj":"disease:C0013264"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T1537","obj":"T1538"},{"id":"R2","pred":"associated_with","subj":"T1537","obj":"T1538"},{"id":"R3","pred":"associated_with","subj":"T1537","obj":"T1538"},{"id":"R4","pred":"associated_with","subj":"T1537","obj":"T1538"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T1537","pred":"source","obj":"DisGeNet-2017-sample"},{"subj":"T1538","pred":"source","obj":"DisGeNet-2017-sample"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"17380205-1#80#90#gene1756","span":{"begin":207,"end":217},"obj":"gene1756"},{"id":"17380205-1#0#27#diseaseC0013264","span":{"begin":127,"end":154},"obj":"diseaseC0013264"},{"id":"17380205-1#29#32#diseaseC0013264","span":{"begin":156,"end":159},"obj":"diseaseC0013264"},{"id":"17380205-1#159#178#diseaseC0234958","span":{"begin":286,"end":305},"obj":"diseaseC0234958"},{"id":"17380205-3#28#31#gene64689","span":{"begin":506,"end":509},"obj":"gene64689"},{"id":"17380205-3#28#31#gene5970","span":{"begin":506,"end":509},"obj":"gene5970"},{"id":"17380205-3#28#31#gene6857","span":{"begin":506,"end":509},"obj":"gene6857"},{"id":"17380205-3#28#31#gene65125","span":{"begin":506,"end":509},"obj":"gene65125"},{"id":"17380205-3#113#116#diseaseC0013264","span":{"begin":591,"end":594},"obj":"diseaseC0013264"}],"relations":[{"id":"80#90#gene17560#27#diseaseC0013264","pred":"associated_with","subj":"17380205-1#80#90#gene1756","obj":"17380205-1#0#27#diseaseC0013264"},{"id":"80#90#gene175629#32#diseaseC0013264","pred":"associated_with","subj":"17380205-1#80#90#gene1756","obj":"17380205-1#29#32#diseaseC0013264"},{"id":"80#90#gene1756159#178#diseaseC0234958","pred":"associated_with","subj":"17380205-1#80#90#gene1756","obj":"17380205-1#159#178#diseaseC0234958"},{"id":"28#31#gene64689113#116#diseaseC0013264","pred":"associated_with","subj":"17380205-3#28#31#gene64689","obj":"17380205-3#113#116#diseaseC0013264"},{"id":"28#31#gene5970113#116#diseaseC0013264","pred":"associated_with","subj":"17380205-3#28#31#gene5970","obj":"17380205-3#113#116#diseaseC0013264"},{"id":"28#31#gene6857113#116#diseaseC0013264","pred":"associated_with","subj":"17380205-3#28#31#gene6857","obj":"17380205-3#113#116#diseaseC0013264"},{"id":"28#31#gene65125113#116#diseaseC0013264","pred":"associated_with","subj":"17380205-3#28#31#gene65125","obj":"17380205-3#113#116#diseaseC0013264"}],"attributes":[{"subj":"17380205-1#80#90#gene1756","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"17380205-1#0#27#diseaseC0013264","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"17380205-1#29#32#diseaseC0013264","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"17380205-1#159#178#diseaseC0234958","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"17380205-3#28#31#gene64689","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"17380205-3#28#31#gene5970","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"17380205-3#28#31#gene6857","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"17380205-3#28#31#gene65125","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"17380205-3#113#116#diseaseC0013264","pred":"source","obj":"DisGeNET5_gene_disease"}]},{"project":"Inflammaging","denotations":[{"id":"T1","span":{"begin":0,"end":126},"obj":"Sentence"},{"id":"T2","span":{"begin":127,"end":306},"obj":"Sentence"},{"id":"T3","span":{"begin":307,"end":477},"obj":"Sentence"},{"id":"T4","span":{"begin":478,"end":595},"obj":"Sentence"},{"id":"T5","span":{"begin":596,"end":860},"obj":"Sentence"},{"id":"T6","span":{"begin":861,"end":980},"obj":"Sentence"},{"id":"T7","span":{"begin":981,"end":1182},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":126},"obj":"Sentence"},{"id":"T2","span":{"begin":127,"end":306},"obj":"Sentence"},{"id":"T3","span":{"begin":307,"end":477},"obj":"Sentence"},{"id":"T4","span":{"begin":478,"end":595},"obj":"Sentence"},{"id":"T5","span":{"begin":596,"end":860},"obj":"Sentence"},{"id":"T6","span":{"begin":861,"end":980},"obj":"Sentence"},{"id":"T7","span":{"begin":981,"end":1182},"obj":"Sentence"}],"attributes":[{"subj":"T1","pred":"source","obj":"Inflammaging"},{"subj":"T2","pred":"source","obj":"Inflammaging"},{"subj":"T3","pred":"source","obj":"Inflammaging"},{"subj":"T4","pred":"source","obj":"Inflammaging"},{"subj":"T5","pred":"source","obj":"Inflammaging"},{"subj":"T6","pred":"source","obj":"Inflammaging"},{"subj":"T7","pred":"source","obj":"Inflammaging"},{"subj":"T1","pred":"source","obj":"Inflammaging"},{"subj":"T2","pred":"source","obj":"Inflammaging"},{"subj":"T3","pred":"source","obj":"Inflammaging"},{"subj":"T4","pred":"source","obj":"Inflammaging"},{"subj":"T5","pred":"source","obj":"Inflammaging"},{"subj":"T6","pred":"source","obj":"Inflammaging"},{"subj":"T7","pred":"source","obj":"Inflammaging"}]},{"project":"PMID_GLOBAL","denotations":[{"id":"T1","span":{"begin":98,"end":125},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":127,"end":154},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":156,"end":159},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":310,"end":313},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":591,"end":594},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T6","span":{"begin":1058,"end":1091},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T7","span":{"begin":1178,"end":1181},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0010679"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"0010679"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"0010679"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"0010679"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"0010679"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"0016106"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"0010679"},{"subj":"T1","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T2","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T3","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T4","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T5","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T6","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T7","pred":"source","obj":"PMID_GLOBAL"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"PubmedHPO","color":"#93c6ec","default":true},{"id":"DisGeNET","color":"#e0ec93"},{"id":"sentences","color":"#de93ec"},{"id":"DisGeNet-2017-sample","color":"#93ecc4"},{"id":"DisGeNET5_gene_disease","color":"#ecaa93"},{"id":"Inflammaging","color":"#9395ec"},{"id":"PMID_GLOBAL","color":"#afec93"}]}]}}