MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F19%3A10400919" target="_blank" >RIV/00216208:11160/19:10400919 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=lGPh32ZGFy" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=lGPh32ZGFy</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms20123107" target="_blank" >10.3390/ijms20123107</a>

Jazyk výsledku

angličtina

Název v původním jazyce

MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells

Popis výsledku v původním jazyce

Upon inflammation, monocyte-derived macrophages (M Phi) infiltrate blood vessels to regulate several processes involved in vascular pathophysiology. However, little is known about the mediators involved. Macrophage polarization is crucial for a fast and efficient initial response (GM-M Phi) and a good resolution (M-M Phi) of the inflammatory process. The functional activity of polarized M Phi is exerted mainly through their secretome, which can target other cell types, including endothelial cells. Endoglin (CD105) is a cell surface receptor expressed by endothelial cells and M Phi that is markedly upregulated in inflammation and critically involved in angiogenesis. In addition, a soluble form of endoglin with anti-angiogenic activity has been described in inflammation-associated pathologies. The aim of this work was to identify components of the M Phi secretome involved in the shedding of soluble endoglin. We find that the GM-M Phi secretome contains metalloprotease 12 (MMP-12), a GM-M Phi specific marker that may account for the anti-angiogenic activity of the GM-M Phi secretome. Cell surface endoglin is present in both GM-M Phi and M-M Phi, but soluble endoglin is only detected in GM-M Phi culture supernatants. Moreover, MMP-12 is responsible for the shedding of soluble endoglin in vitro and in vivo by targeting membrane-bound endoglin in both M Phi and endothelial cells. These data demonstrate a direct correlation between GM-M Phi polarization, MMP-12, and soluble endoglin expression and function. By targeting endothelial cells, MMP-12 may represent a novel mediator involved in vascular homeostasis.

Název v anglickém jazyce

MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells

Popis výsledku anglicky

Upon inflammation, monocyte-derived macrophages (M Phi) infiltrate blood vessels to regulate several processes involved in vascular pathophysiology. However, little is known about the mediators involved. Macrophage polarization is crucial for a fast and efficient initial response (GM-M Phi) and a good resolution (M-M Phi) of the inflammatory process. The functional activity of polarized M Phi is exerted mainly through their secretome, which can target other cell types, including endothelial cells. Endoglin (CD105) is a cell surface receptor expressed by endothelial cells and M Phi that is markedly upregulated in inflammation and critically involved in angiogenesis. In addition, a soluble form of endoglin with anti-angiogenic activity has been described in inflammation-associated pathologies. The aim of this work was to identify components of the M Phi secretome involved in the shedding of soluble endoglin. We find that the GM-M Phi secretome contains metalloprotease 12 (MMP-12), a GM-M Phi specific marker that may account for the anti-angiogenic activity of the GM-M Phi secretome. Cell surface endoglin is present in both GM-M Phi and M-M Phi, but soluble endoglin is only detected in GM-M Phi culture supernatants. Moreover, MMP-12 is responsible for the shedding of soluble endoglin in vitro and in vivo by targeting membrane-bound endoglin in both M Phi and endothelial cells. These data demonstrate a direct correlation between GM-M Phi polarization, MMP-12, and soluble endoglin expression and function. By targeting endothelial cells, MMP-12 may represent a novel mediator involved in vascular homeostasis.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

International Journal of Molecular Sciences

ISSN

1422-0067

e-ISSN

—

Svazek periodika

20

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

19

Strana od-do

3107

Kód UT WoS článku

000473756000257

EID výsledku v databázi Scopus

2-s2.0-85068924393