Abstract：
Visceral myopathy (VSCM) is a rare genetic disease, orphan of pharmacological therapy. VSCM diagnosis is not always straightforward due to symptomatology similarities with mitochondrial or neuronal forms of intestinal pseudo-obstruction. The most prevalent form of VSCM is associates with variants in the gene ACTG2, encoding the protein gamma-2 actin. Overall, VSCM is a mechano-biological disorder, in which different genetic variants lead to similar alterations to the contractile phenotype of enteric smooth muscles, resulting in the emergence of life-threatening symptoms. In this work we analyzed the morpho-mechanical phenotype of human dermal fibroblasts from patients affected with VSCM, demonstrating that they retain a clear signature of the disease when compared with different controls. We evaluated several biophysical traits of fibroblasts, and we show that a measure of cellular traction forces can be used as a non-specific biomarker of the disease. We propose that a simple assay based on traction forces could be designed to provide a valuable support for clinical decision or pre-clinical research.
摘要：
内脏肌病（VSCM）是一种罕见的遗传性疾病，药物治疗的孤儿。由于与线粒体或神经元形式的肠假性梗阻的症状学相似性，VSCM诊断并不总是简单的。VSCM的最普遍形式是与编码蛋白γ-2肌动蛋白的基因ACTG2中的变体相关。总的来说,VSCM是一种机械生物学障碍，其中不同的遗传变异导致类似的改变肠平滑肌的收缩表型，导致出现危及生命的症状。在这项工作中，我们分析了受VSCM影响的患者的人真皮成纤维细胞的形态机械表型，证明与不同的对照相比，它们保留了明确的疾病特征。我们评估了成纤维细胞的几种生物物理特征，我们证明了细胞牵引力的测量可以用作疾病的非特异性生物标志物。我们建议可以设计基于牵引力的简单测定法，为临床决策或临床前研究提供有价值的支持。
