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

Pitrez, Patricia R, Estronca, Luis, Monteiro, Luis Miguel, Colell, Guillem, Vazao, Helena, Santinha, Deolinda, Harhouri, Karim, Thornton, Daniel, Navarro, Claire, Egesipe, Anne-Laure
et al (show 11 more authors) (2020) Vulnerability of progeroid smooth muscle cells to biomechanical forces is mediated by MMP13. NATURE COMMUNICATIONS, 11 (1). 4110-.

Access the full-text of this item by clicking on the Open Access link.


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<sup>G609G/G609G</sup>Mmp13<sup>-/-</sup> mice or Lmna<sup>G609G/G609G</sup>Mmp13<sup>+/+</sup> 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.

Item Type: Article
Uncontrolled Keywords: Myocytes, Smooth Muscle, Animals, Mice, Mice, Mutant Strains, Cardiovascular Diseases, Progeria, Lamin Type A, Proteomics, Biotechnology, Heart Rate, Female, Male, Matrix Metalloproteinase 13, Induced Pluripotent Stem Cells, Matrix Metalloproteinase Inhibitors
Depositing User: Symplectic Admin
Date Deposited: 28 Aug 2020 10:34
Last Modified: 18 Jan 2023 23:35
DOI: 10.1038/s41467-020-17901-2
Open Access URL:
Related URLs: