Patient's dermal fibroblasts as disease markers for visceral myopathy

患者的真皮成纤维细胞作为内脏肌病的疾病标志物

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作者:Federica Viti, Francesca Micaela Pramotton, Michela Martufi, Raffaella Magrassi, Nicoletta Pedemonte, Mario Nizzari, Francesca Cella Zanacchi, Benedetta De Michele, Manuela Alampi, Martina Zambito, Giuseppe Santamaria, Adriana Bajetto, Sabah Sardar, Valeria Tomati, Paolo Gandullia, Costanza Giampiet

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.

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