The expression of gene ANKRD1 correlates with hypoxia status in muscle biopsies of treatment-näive adult dermatomyositis

Abstract

OBJECTIVES. The ANKRD1 gene codes for the ankyrin repeat domain containing protein 1 and has an important role in myogenesis and possibly also in angiogenesis. Microvasculopathy is a cornerstone and an early pathological marker of change in dermatomyositis, leading to hypoxia and muscle perifascicular atrophy. These alterations could upregulate genes involved in myogenesis and angiogenesis such as ANKRD1. Therefore, we analyzed ANKRD1 expression in muscle biopsies of dermatomyositis and correlated with other hypoxia parameters and with histological changes. METHODS. Total RNA was extracted from frozen muscle biopsies samples of 29 dermatomyositis patients. A control group consisted of 20 muscle biopsies from adult patients with non-inflammatory myopathy diseases. The gene coding for hypoxia-inducible factor 1, alpha subunit (HIF1A), was analyzed to estimate the degree of hypoxia. ANKRD1 and HIF1A transcript expression levels were determined by quantitative real time PCR. RESULTS. Significantly higher ANKRD1 and HIF1A expression levels were observed in dermatomyositis relative to the control group (P<0.001, both genes). In addition, ANKRD1 and HIF1A were coexpressed (r=0.703, P=0.001) and their expression levels correlated positively to perifascicular atrophy (r=0.420, P=0.023 and r=0.404, P=0.030, respectively). CONCLUSIONS. Our results demonstrate ANKRD1 overexpression in dermatomyositis correlated to HIF1A expression and perifascicular atrophy. ANKRD1 involvement in myogenesis and angiogenesis mechanisms indicates that further investigation is worthwhile.

A Review of Genes Involved in Wound Healing

“…VEGF and iNOS genes could be regulated by HIF1-α which is capable of activating multiple members of the VEGF family, improving revascularization and the rate of wound healing ( 48 ). Recently, the effects of transcriptional cofactors and cardiac adriamycin-responsive protein (CARP) have been studied in terms of the evaluation of potent effects on wound neovascularization and endothelial migration in several animal models ( 49 ). Additionally, cell signaling processes such as SMAD proteins have been proven to have a significant role in regulating inflammation in chondrocyte differentiation and cutaneous tissue repair.…”

Alta prevalência de padrão de miopatia necrosante em biópsias musculares de pacientes com síndrome antissintetase com autoanticorpos Anti-Jo-1 positivo

“…• Sexo, idade ao início da doença, raça, tempo entre o início de sintomas e o diagnóstico da doença; SHINJO et al, 2015). A biópsia muscular é realizada apenas em paciente com acometimento muscular definido.…”

“…Não encontramos associação entre idade, sexo, etnia, manifestações clínicas ou dados laboratoriais quando comparamos o padrão histológico de miopatia necrosante com outros padrões histológicos. Estudos prévios já descreveram a não associação entre características clínicas e parâmetros histopatológicos em biópsias musculares (SHINJO et al, 2015;DIAZ et al, 2017;LUNDBERG et al, 2000). Tal fato pode ser justificado devido ao fato de que infiltrados inflamatórios histológicos podem ocorrer em focos, justificando uma dissociação entre parâmetros clínicos e características histológicas.…”

“…Reconhecemos plenamente as limitações decorrentes do fato de que nem todos os pacientes haviam se abstido de terapia no momento da biópsia muscular; levantando a possibilidade de que pode ter influenciado a apresentação histológica. Apesar das preocupações de que a introdução precoce de glicocorticoide possa interferir no processo inflamatório nos tecidos musculares, o uso prévio de glicocorticoide não parece influenciar a presença ou o grau de infiltrados inflamatórios em biópsias musculares em pacientes com atividade clínica e laboratorial da doença (SHINJO et al, 2015;DIAZ et al, 2017;PINHATA et al, 2015).…”