Unknown

Dataset Information

0

Repressor and activator protein accelerates hepatic ischemia reperfusion injury by promoting neutrophil inflammatory response.


ABSTRACT: Repressor and activator protein (Rap1) directly regulates nuclear factor-?B (NF-?B) dependent signaling, which contributes to hepatic IRI. We here intended to investigate the effect of Rap1 in hepatic ischemia reperfusion injury (IRI) and to explore the underlying mechanisms. The association of Rap1 expression with hepatic inflammatory response were investigated in both human and rat liver transplantation. The effect of Rap1 in hepatic IRI was studied in Rap1 knockout mice IRI model in vivo and primary cells in vitro. Our results showed that over expression of Rap1 was associated with severe liver graft inflammatory response, especially in living donor liver transplantation. The results were also validated in rat liver transplantation model. In mice hepatic IRI model, the knockout of Rap1 reduced hepatic damage and hepatic inflammatory response. In primary cells, the knockout of Rap1 suppressed neutrophils migration activity and adhesion in response to liver sinusoidal endothelial cells through down-regulating neutrophils F-Actin expression and CXCL2/CXCR2 pathway. In addition, the knockout of Rap1 also decreased production of pro-inflammatory cytokines/chemokines in primary neutrophils and neutrophils-induced hepatocyte damage. In conclusion, Rap1 may induce hepatic IRI through promoting neutrophils inflammatory response. Rap1 may be the potential therapeutic target of attenuating hepatic IRI.

SUBMITTER: Li CX 

PROVIDER: S-EPMC5053682 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

Repressor and activator protein accelerates hepatic ischemia reperfusion injury by promoting neutrophil inflammatory response.

Li Chang Xian CX   Lo Chung Mau CM   Lian Qizhou Q   Ng Kevin Tak-Pan KT   Liu Xiao Bing XB   Ma Yuen Yuen YY   Qi Xiang X   Yeung Oscar Wai Ho OW   Tergaonkar Vinay V   Yang Xin Xiang XX   Liu Hui H   Liu Jiang J   Shao Yan Y   Man Kwan K  

Oncotarget 20160501 19


Repressor and activator protein (Rap1) directly regulates nuclear factor-κB (NF-κB) dependent signaling, which contributes to hepatic IRI. We here intended to investigate the effect of Rap1 in hepatic ischemia reperfusion injury (IRI) and to explore the underlying mechanisms. The association of Rap1 expression with hepatic inflammatory response were investigated in both human and rat liver transplantation. The effect of Rap1 in hepatic IRI was studied in Rap1 knockout mice IRI model in vivo and  ...[more]

Similar Datasets

| S-EPMC4401083 | biostudies-literature
| S-EPMC3094027 | biostudies-literature
| S-EPMC10076300 | biostudies-literature
| S-EPMC3012573 | biostudies-literature
| S-EPMC3736708 | biostudies-literature
| S-EPMC8171082 | biostudies-literature
| S-EPMC9616812 | biostudies-literature
| S-EPMC10313896 | biostudies-literature
| S-EPMC6948758 | biostudies-literature
| S-EPMC2632727 | biostudies-literature