Abstract:
: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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Pitrez PR,Estronca L,Monteiro LM,Colell G,Vazão H,Santinha D,Harhouri K,Thornton D,Navarro C,Egesipe AL,Carvalho T,Dos Santos RL,Lévy N,Smith JC,de Magalhães JP,Ori A,Bernardo A,De Sandre-Giovannoli A,Nissan X,Roseldoi
10.1038/s41467-020-17901-2subject
Has Abstractpub_date
2020-08-17 00:00:00pages
4110issue
1issn
2041-1723pii
10.1038/s41467-020-17901-2journal_volume
11pub_type
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