Fibronectin extra domain a limits liver dysfunction and protects mice during acute inflammation.
Atheroscler Plus
; 52: 23-31, 2023 Jun.
Article
em En
| MEDLINE
| ID: mdl-37287804
ABSTRACT
Background and aim:
The primary transcript of fibronectin (FN) undergoes alternative splicing to generate different isoforms, including FN containing the Extra Domain A (FN_EDA+), whose expression is regulated spatially and temporarily during developmental and disease conditions including acute inflammation. The role of FN_EDA+ during sepsis, however, remains elusive.Methods:
Mice constitutively express the EDA domain of fibronectin (EDA+/+); lacking the FN EDA domain (EDA-/-) or with a conditional ablation of EDA + inclusion only in liver produced FN (alb-CRE+EDA floxed mice) thus expressing normal plasma FN were used. Systemic inflammation and sepsis were induced by either LPS injection (70 mg/kg) or by cecal ligation and puncture (CLP) Neutrophils isolated from septic patients were tested for neutrophil binding ability.Results:
We observed that EDA+/+ were protected toward sepsis as compared to EDA-/- mice. Also alb-CRE+EDA floxed mice presented reduced survival, thus indicating a key role for EDA in protecting toward sepsis. This phenotype was associated with improved liver and spleen inflammatory profile. Ex vivo experiments showed that neutrophils bind to a larger extent to an FN_EDA + coated surface as compared to FN, thus potentially limiting their over-reactivity.Conclusions:
Our study demonstrates that the inclusion of the EDA domain in fibronectin dampens the nflammatoryi consequences of sepsis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Atheroscler Plus
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Canadá