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PLoS One ; 15(7): e0235784, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32658899

RESUMEN

Soft tissue is composed of cells surrounded by an extracellular matrix that is made up of a diverse array of intricately organized proteins. These distinct components work in concert to maintain homeostasis and respond to tissue damage. During tissue repair, extracellular matrix proteins and their degradation products are known to influence physiological processes such as angiogenesis and inflammation. In this study we developed a discovery platform using a decellularized extracellular matrix biomaterial to identify new chemotrophic factors derived from the extracellular matrix. An in vitro culture of RAW.264 macrophage cells with the biomaterial ovine forestomach matrix led to the identification of a novel ~12 kDa chemotactic factor, termed 'MayDay', derived from the N-terminal 31-188 sequence of decorin. The recombinant MayDay protein was shown to be a chemotactic agent for mesenchymal stromal cells in vitro and in vivo. We hypothesize that the macrophage-induced cleavage of decorin, via MMP-12, leads to the release of the chemotactic molecule MayDay, that in turn recruits cells to the site of damaged tissue.


Asunto(s)
Factores Quimiotácticos/farmacología , Decorina/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Secuencia de Aminoácidos , Animales , Células Cultivadas , Factores Quimiotácticos/química , Quimiotaxis/efectos de los fármacos , Decorina/química , Células Madre Mesenquimatosas/citología , Ratones , Fragmentos de Péptidos/química , Células RAW 264.7 , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacología , Ovinos
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