Overexpression of Ankyrin Repeat Domain Containing Protein 1 Gene (ANKRD1) in Dermatomyositis Muscle Biopsies Is Correlated to Hypoxia and Perifascicular Atrophy

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorSHINJO, Samuel K.
dc.contributor.authorOBA-SHINJO, Sueli M.
dc.contributor.authorUNO, Miyuki
dc.contributor.authorMARIE, Suely K. N.
dc.date.accessioned2013-10-11T21:22:54Z
dc.date.available2013-10-11T21:22:54Z
dc.date.issued2012
dc.description.abstractBackground/Purpose: ANKRD1 codes for ankyrin repeat domain containing protein 1, which belongs to the muscle ankyrin repeat protein family involved in a mechano-signaling pathway that links myofibrillar stress response to muscle gene expression. In addition, ANKRD1 has an important role in transcriptional regulation, myofibrillar assembly, cardio-genesis, myogenesis and also possibly in angiogenesis. Microvasculopathy is considered as a cornerstone and early pathological change in dermatomyositis (DM), leading to hypoxia, capillary necrosis and muscle perifascicular atrophy. These alterations could upregulate genes involved in myogenesis and angiogenesis like ANKRD1. Therefore, we analyzed ANKRD1 expression in muscle biopsies of DM patients and correlated with other hypoxia parameters. Methods: RNA was extracted from frozen muscle biopsies samples of 30 untreated adult DM patients (Bohan and Peter’s criteria, 1975). As a control group, we analyzed 20 muscle biopsies with no histological change from untreated adult patients with non-inflammatory myopathy diseases. The gene coding for hypoxia-inducible factor 1, alpha subunit (HIF1A) was analyzed to estimate hypoxia degree. The ANKRD1 and HIF1A transcript expression levels were determined by quantitative real time PCR using Sybr Green method. Perifascicular atrophy was analyzed histologically by semi-quantitative method of HE stained biopsies. Expression and localization of ANKRD1 and HIF1a in muscle biopsies was accessed by immunohistochemistry. Results: Higher ANKRD1 and HIF1A expressions levels were observed in DM relative to control group (p<0.001 and p<0.001). In addition, the expression levels of both genes were correlated (r=0.703, P=0.001). We also observed a positive correlation of both genes to perifascicular atrophy (r=0.420, p=0.023 and r=0.404, p=0.030, respectively). However, ANKRD1 and HIF1A expression levels did not correlate to demographic, clinical and laboratory features (p>0.05). Immunohistochemistry showed that ANKRD1 and HIF1a were expressed mainly by atrophic muscle perifascicular cells. Conclusion: Our results demonstrated ANKRD1 is overexpressed, correlated to HIF1A in perifascicular atrophic fibers of DM muscle specimens. ANKRD1 involvement in myogenesis and angiogenesis mechanism will be further investigated.
dc.description.conferencedateNOV 09-14, 2012
dc.description.conferencelocalWashington - DC, EUA
dc.description.conferencenameAnnual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP)
dc.description.indexMEDLINE
dc.identifier.citationARTHRITIS AND RHEUMATISM, v.64, n.10, suppl.S, p.S823-S823, 2012
dc.identifier.doi10.1002/art.37735
dc.identifier.issn0004-3591
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/2909
dc.language.isoeng
dc.publisherWILEY-BLACKWELL
dc.relation.ispartofArthritis and Rheumatism
dc.rightsrestrictedAccess
dc.rights.holderCopyright WILEY-BLACKWELL
dc.subject.wosRheumatology
dc.titleOverexpression of Ankyrin Repeat Domain Containing Protein 1 Gene (ANKRD1) in Dermatomyositis Muscle Biopsies Is Correlated to Hypoxia and Perifascicular Atrophy
dc.typeconferenceObject
dc.type.categorymeeting abstract
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.contributor.author-fmusphcSAMUEL KATSUYUKI SHINJO
hcfmusp.contributor.author-fmusphcSUELI MIEKO OBA SHINJO
hcfmusp.contributor.author-fmusphcMIYUKI UNO
hcfmusp.contributor.author-fmusphcSUELY KAZUE NAGAHASHI MARIE
hcfmusp.description.beginpageS823
hcfmusp.description.endpageS823
hcfmusp.description.issue10
hcfmusp.description.issuesuppl S
hcfmusp.description.volume64
hcfmusp.origemWOS
hcfmusp.origem.wosWOS:000309748304216
hcfmusp.publisher.cityHOBOKEN
hcfmusp.publisher.countryUSA
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relation.isAuthorOfPublication6db493d7-f88b-41d2-bdf6-ff0ffaa44a54
relation.isAuthorOfPublicationf6a8a86c-977d-4706-a6cc-8879ecbde0c7
relation.isAuthorOfPublication97df2bf7-eb85-4fff-a1dc-d2d1fe781489
relation.isAuthorOfPublication.latestForDiscovery07f179c5-58d8-4efe-832c-52095a9009d6
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