VULNERABILITY OF PROGEROID SMOOTH MUSCLE CELLS TO ARTERIAL SHEAR STRESS IS MEDIATED BY MMP13
Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disease in children that leads to early death. Smooth muscle cells (SMCs) are the most affected cells in HGPS individuals, although the reason for such vulnerability remains poorly understood. In this work, we develop a microfluidic ch...
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| Veröffentlicht in: | Nature communications 2022, Vol.28 (1) |
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| creator | Pitrez, Patricia Estronca, Luis Monteiro, Luis Colell, Guillem Vazão, Helena Santinha, Deolinda Harhouri, Karim Thornton, Daniel Navarro, Claire L. Egesipe, Anne-Laure Cavalho, Tania dos Santos, Rodrigo L Levy, Nicolas Smith, James Magalhaes, Joao-Pedro Ori, Alessandro Bernardo, Andreia de Sandre-Giovannoli, Annachiara Nissan, Xavier Rosell, Anna Ferreira, Lino |
| description | Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disease in children that leads to early death. Smooth muscle cells (SMCs) are the most affected cells in HGPS individuals, although the reason for such vulnerability remains poorly understood. In this work, we develop a microfluidic chip formed by HGPS-SMCs generated from induced pluripotent stem cells (iPSCs), to study their vulnerability to flow shear stress. HGPS-iPSC SMCs cultured under arterial flow conditions detach from the chip after a few days of culture; this process is mediated by the upregulation of metalloprotease 13 (MMP13). Importantly, double-mutant LmnaG609G/G609GMmp13−/− mice or LmnaG609G/G609GMmp13+/+ mice treated with a MMP inhibitor show lower SMC loss in the aortic arch than controls. MMP13 upregulation appears to be mediated, at least in part, by the upregulation of glycocalyx. Our HGPS-SMCs chip represents a platform for developing treatments for HGPS individuals that may complement previous pre-clinical and clinical treatments. |
| doi_str_mv | 10.1038/s41467-020-17901-2 |
| format | Article |
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| subjects | Genetics Life Sciences |
| title | VULNERABILITY OF PROGEROID SMOOTH MUSCLE CELLS TO ARTERIAL SHEAR STRESS IS MEDIATED BY MMP13 |
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