Vulnerability of progeroid smooth muscle cells to biomechanical forces is mediated by MMP13.

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 Lmna^G609G/G609GMmp13^-/- mice or Lmna^G609G/G609GMmp13^+/+ mice treated with a MMP inhibitor show lower SMC loss in the ao

SUBMITTER: Pitrez PR 

PROVIDER: S-EPMC7431909 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature