Study of NFAT5 Physiology in Duchenne Muscular Dystrophy Fibroblasts: Provisionary Explanation for the Permanent Fibrosis Formation in Duchenne Muscular Dystrophy | Chapter 6 | Recent Research Advances in Biology Vol. 9

 Chronic inflammation and fibrotic tissue development by fibroblasts characterise Duchenne muscular dystrophy (DMD). Nuclear factor of activated T-cells 5 (NFAT5), a promyogenic factor that responds to hyperosmolar or pro-inflammatory stress, is essentially present in all cells. The lack of NFAT5 causes cell cycle arrest in embryogenic fibroblasts. Unaffected skeletal muscle fibroblasts from one healthy donor demonstrated NFAT5 nuclear translocation and normal cell survival when exposed to hyperosmolar stress. Under pro-inflammatory conditions, the absence of NFAT5 translocation resulted in a reduction in cell proliferation (Incucyte ZOOM). In one DMD patient's skeletal muscle fibroblasts, The nucleus was the only place where NFAT5 was found. The physiology of NFAT5 was unaffected by hyperosmolar circumstances or pro-inflammatory cytokines IFN-, IL-1, and TNF- (immunofluorescence, western blotting, RT-qPCR). In undisturbed cell development, hyperosmolarity resulted in lower cell viability and pro-inflammatory stress. These data imply that NFAT5 is required for the survival of DMD fibroblasts. When DMD fibroblasts are exposed to pro-inflammatory or hyperosmolar stress, an unexpected NFAT5 response occurs, in which fibroblasts are not triggered by inflammatory cytokines and cannot resist hyperosmolarity. Chronic inflammation can be thought of as a non-restrictive element in the development of cancer. Fibrosis is a complication of DMD. Permanent fibrotic matrix synthesis by DMD cells could be explained molecularly by abnormal NFAT5 physiology.

 
Author (s) Details

Sandrine Herbelet
Department of Neurology, Ghent University and Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.

Boel De Paepe
Department of Neurology, Ghent University and Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium and Neuromuscular Reference Center, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.

Jan L. De Bleecker
Department of Neurology, Ghent University and Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium and Neuromuscular Reference Center, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.

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