Inserm, Institut national de la santé et de la recherche médicale
Faculté de pharmacie, Aix Marseille Université

Accueil » Le labo » Thématiques de recherche » Physiopathologie de l’endothélium » Rôle de CD146 dans l’inflammation et l’angiogénèse » Rôle de CD146 dans l’inflammation et l’angiogenèse

Rôle de CD146 dans l’inflammation et l’angiogenèse

Our goal is to understand the role of CD146/CD146s in inflammation and angiogenesis and to develop diagnostic and therapeutic strategies targeting CD146/sCD146.

CD146, which was initially described on the metastatic melanoma has been identified by our team as a new inter- endothelial adhesion molecule. It exists as short and long membrane isoforms and as a soluble form (sCD146) detectable in the circulating blood. We recently demonstrated that CD146/sCD146 regulate permeability, transmigration of monocytes and displays angiogenic properties.

The team

Marcel Blot-Chabaud (DR), Nathalie Bardin (MCU -PH), Aurélie Leroyer (MCU), Alexandrine Bertaut (MCU), Richard Bachelier (Ingénieur recherche), Alexandre Muller (Ingénieur étude), Karim Fallague (TR), Marie Nollet (doctorant), Sylvie Bouvier (doctorant), Jimmy Stalin (doctorant), Amel Essaadi (doctorant), Muriel Blin (doctorant).

Main publications

Patents

Grants

ANR, SATT Sud-Est, Fondation de France, Agence de Biomédecine.

Biological role

Biological role of CD146/CD146s

Functions
We focus our study on the role of CD146/CD146s in inflammation and physiological/pathological angiogenesis, with a main interest in tumoral and obstetrical angiogenesis. To help us in this task, we have generated mice with a conditional knockout of CD146 which are viable and validated by the absence of CD146 staining of the vessels in different organs. Lung endothelial cells (LMEC) were isolated from this model for in vitro study of the functions of CD146 (CD146KO-LMEC).

Partners
The identification of ligands and intracellular interaction partners of CD146 is essential to better understand its mechanism of action. We have identified galectin 1 and angiomotin as CD146/CD146s partners. Other proteins interacting with CD146/CD146s are currently under investigation.

Generation of soluble CD146
The generation of the soluble form of CD146 may result either from a membrane proteolysis or alternate splicing of CD146. The two mechanisms are currently under study.

Biomarker therapeutic strategies

Biomarker and therapeutic strategies targeting CD146

Biomarker
We investigate whether changes in circulating levels of soluble CD146 could identify alterations related to inflammatory and /or angiogenic dysregulations. We also identified auto-antibodies directed against CD146. Their relevance and modulation in pathology are under investigation.

Therapeutic strategies
Our work has shown that sCD146 displays chemotactic properties on endothelial cells, particularly on endothelial progenitors, and stimulates their proliferation and migration. Administration of sCD146 promotes revascularization in an animal model of hindlimb ischemia. In view of these data, we decided develop angiogenic/anti-angiogenic therapeutic strategies, including generation of anti-CD146 antibodies.