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Título: Overexpression of Ankyrin Repeat Domain Containing Protein 1 Gene (ANKRD1) in Dermatomyositis Muscle Biopsies Is Correlated to Hypoxia and Perifascicular Atrophy
Autor: SHINJO, Samuel K.OBA-SHINJO, Sueli M.UNO, MiyukiMARIE, Suely K. N.
Citación: ARTHRITIS AND RHEUMATISM, v.64, n.10, suppl.S, p.S823-S823, 2012
Resumen: Background/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.
Aparece en las colecciones:

Comunicações em Eventos - FM/MNE
Departamento de Neurologia - FM/MNE

Comunicações em Eventos - HC/ICESP
Instituto do Câncer do Estado de São Paulo - HC/ICESP

Comunicações em Eventos - HC/ICHC
Instituto Central - HC/ICHC

Comunicações em Eventos - LIM/15
LIM/15 - Laboratório de Investigação em Neurologia

Comunicações em Eventos - LIM/17
LIM/17 - Laboratório de Investigação em Reumatologia

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