Please use this identifier to cite or link to this item:
https://hdl.handle.net/2445/194621
Title: | Macrophages promote endothelial-to-mesenchymal transition via MT1-MMP/ TGF$\beta 1$ after myocardial infarction |
Author: | Alonso-Herranz, Laura Sahún-Español, Álvaro Paredes, Ana Gonzalo, Pilar Gkontra, Polyxeni Núñez, Vanessa Clemente, Cristina Cedenilla, Marta Villalba-Orero, María Inserte, Javier García-Dorado, David García Arroyo, Alicia Ricote, Mercedes |
Keywords: | Infart de miocardi Codi genètic Cultiu cel·lular Malalties cardiovasculars Myocardial infarction Genetic code Cell culture Cardiovascular diseases |
Issue Date: | 16-Oct-2020 |
Publisher: | eLife Sciences |
Abstract: | Macrophages (M $\varphi s$ ) produce factors that participate in cardiac repair and remodeling after myocardial infarction (MI); however, how these factors crosstalk with other cell types mediating repair is not fully understood. Here we demonstrated that cardiac M $\varphi$ s increased the expression of Mmp14 (MT1-MMP) 7 days post-MI. We selectively inactivated the $M m p 14$ gene in $\mathrm{M} \varphi$ s using a genetic strategy (Mmp14ff: Lyz2-Cre). This conditional KO (MAC-Mmp14 KO) resulted in attenuated post-MI cardiac dysfunction, reduced fibrosis, and preserved cardiac capillary network. Mechanistically, we showed that MT1-MMP activates latent TGF $\beta 1$ in M $\varphi$ s, leading to paracrine SMAD2-mediated signaling in endothelial cells (ECs) and endothelial-to-mesenchymal transition (EndMT). Post-MI MAC-Mmp14 KO hearts contained fewer cells undergoing EndMT than their wild-type counterparts, and Mmp14-deficient $\mathrm{M} \varphi \mathrm{s}$ showed a reduced ability to induce EndMT in co-cultures with ECs. Our results indicate the contribution of EndMT to cardiac fibrosis and adverse remodeling post-MI and identify M $\varphi$ MT1-MMP as a key regulator of this process. |
Note: | Reproducció del document publicat a: https://doi.org/10.7554/eLife.57920 |
It is part of: | eLife, 2020 |
URI: | https://hdl.handle.net/2445/194621 |
Related resource: | https://doi.org/10.7554/eLife.57920 |
ISSN: | 2050-084X |
Appears in Collections: | Articles publicats en revistes (Matemàtiques i Informàtica) |
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