Dataset Information

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 patients, although the reason for such vulnerability remains poorly understood. In this work, we developed a chip formed from HGPS-SMCs that were generated from induced pluripotent stem cells (iPSCs) to study their vulnerability to flow shear stress. HGPS-iPSC SMCs cultured under arterial flow conditions detached from the chip after a few days of culture; this process was mediated by the up-regulation of metalloprotease 13 (MMP13). Importantly, double mutant LmnaG609G/G609GMmp13-/- mice or LmnaG609G/G609GMmp13+/+ mice treated with a MMP inhibitor showed lower SMC loss in the aortic arch than controls. MMP13 up-regulation appears to be mediated by the up-regulation of heparan sulfate, a glycocalyx component. Our results offer a new platform for developing treatments for HGPS patients that may complement previous pre-clinical and clinical treatments.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Aorta

SUBMITTER: Alessandro Ori

LAB HEAD: Alessandro Ori

PROVIDER: PXD011652 | Pride | 2020-08-24

REPOSITORIES: Pride

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			Action	DRS
	180601_JMK_DL_aortic_arch_KIHT_DIA_1.raw	Raw
	180601_JMK_DL_aortic_arch_KIHT_DIA_20.raw	Raw
	180601_JMK_DL_aortic_arch_KIHT_DIA_21.raw	Raw
	180601_JMK_DL_aortic_arch_KIHT_DIA_22.raw	Raw
	180601_JMK_DL_aortic_arch_KIHT_DIA_23.raw	Raw

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

Pitrez Patricia R PR Estronca Luís L Monteiro Luís Miguel LM Colell Guillem G Vazão Helena H Santinha Deolinda D Harhouri Karim K Thornton Daniel D Navarro Claire C Egesipe Anne-Laure AL Carvalho Tânia T Dos Santos Rodrigo L RL Lévy Nicolas N Smith James C JC de Magalhães João Pedro JP Ori Alessandro A Bernardo Andreia A De Sandre-Giovannoli Annachiara A Nissan Xavier X Rosell Anna A Ferreira Lino L

Nature communications 20200817 1

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 ...[more]

PMID: 32807790

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