Nowak Roman, Kwiecien Magdalena, Tkacz Magdalena, Mazurek Urszula
Department of Orthopedics, School of Medicine with the Division of Dentistry, Medical University of Silesia, Wojewódzki Szpital Specjalistyczny nr 5 Plac Medyków 1, 41-200 Sosnowiec, Poland.
Department of Molecular Biology, Medical University of Silesia, Ulica Narcyzów 1, 41-100 Sosnowiec, Poland.
Biomed Res Int. 2014;2014:594287. doi: 10.1155/2014/594287. Epub 2014 Sep 15.
Most researchers agree that idiopathic scoliosis (IS) is a multifactorial disease influenced by complex genetic and environmental factors. The onset of the spinal deformity that determines the natural course of the disease, usually occurs in the juvenile or adolescent period. Transforming growth factors β (TGF-βs) and their receptors, TGFBRs, may be considered as candidate genes related to IS susceptibility and natural history. This study explores the transcriptional profile of TGF-βs, TGFBRs, and TGF-β responsive genes in the paravertebral muscles of patients with juvenile and adolescent idiopathic scoliosis (JIS and AIS, resp.). Muscle specimens were harvested intraoperatively and grouped according to the side of the curve and the age of scoliosis onset. The results of microarray and qRT-PCR analysis confirmed significantly higher transcript abundances of TGF-β2, TGF-β3, and TGFBR2 in samples from the curve concavity of AIS patients, suggesting a difference in TGF-β signaling in the pathogenesis of juvenile and adolescent curves. Analysis of TGF-β responsive genes in the transcriptomes of patients with AIS suggested overrepresentation of the genes localized in the extracellular region of curve concavity: LTBP3, LTBP4, ITGB4, and ITGB5. This finding suggests the extracellular region of paravertebral muscles as an interesting target for future molecular research into AIS pathogenesis.
大多数研究人员认为,特发性脊柱侧凸(IS)是一种受复杂遗传和环境因素影响的多因素疾病。决定疾病自然病程的脊柱畸形通常在青少年期发病。转化生长因子β(TGF-βs)及其受体TGFBRs可被视为与IS易感性和自然病程相关的候选基因。本研究探讨青少年特发性脊柱侧凸(分别为JIS和AIS)患者椎旁肌中TGF-βs、TGFBRs和TGF-β反应性基因的转录谱。术中采集肌肉标本,并根据侧弯侧和脊柱侧凸发病年龄进行分组。微阵列和qRT-PCR分析结果证实,AIS患者侧弯凹侧样本中TGF-β2、TGF-β3和TGFBR2的转录丰度显著更高,提示青少年和青少年曲线发病机制中TGF-β信号存在差异。对AIS患者转录组中TGF-β反应性基因的分析表明,位于侧弯凹侧细胞外区域的基因(LTBP3、LTBP4、ITGB4和ITGB5)过度表达。这一发现表明,椎旁肌的细胞外区域是未来AIS发病机制分子研究的一个有趣靶点。