Effect of hypoxia-inducible factor-1t expression in toll-like receptor 4 signaling pathway-mediated rat lung ischemia-reperfusion injury and possible mechanism
10.3760/cma.j.issn.0254-1785.2014.09.012
- VernacularTitle:缺氧诱导因子-1α在TLR4信号通路介导的大鼠肺缺血再灌注损伤中的影响
- Author:
Zhiyi ZHOU
;
Xingfeng ZHU
;
Jingyu CHEN
;
Qing GUO
;
Guoyi YANG
- Publication Type:Journal Article
- Keywords:
Rats;
Lung;
Reperfusion injury;
Toll-like receptor 4;
Hypoxia-inducible factor-1α
- From:
Chinese Journal of Organ Transplantation
2014;35(9):561-566
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of hypoxia-inducible factor-1α expression (HIF-1α) on toll-like receptor 4 (TLR4) signaling pathway-mediated rat lung ischemia-reperfusion injury (LIRI).Method Forty-five S-D rats were randomly divided into Sham group,LIRI group,LIRI+ TLR4-activated group,LIRI+ TLR4-inhibited group,LIRI + ASK1-inhibited group,LIRI + p38-inhibited group,and LIRI + HIF-1α-inhibited group.The interaction between TLR4 signaling pathway [including TLR4,myeloid differentiation factor 88 (MyD88),TIR-domain-containing adapter-inducing interferon-βTIR-domain-containing adapter-inducing interferon-β (TRIF),Apoptosis signal-regulating kinase 1 (ASK1) and p38] and HIF-1α and the role of TLR4-dependent HIF-1α in LIRI in vivo were analyzed.Result In LIRI,HIF-1α accumulation was induced in a TLR4-dependent fashion,and MyD88,but not TRIF,and activation of ASK1 and P38 were found to be critical for TLR4-mediated HIF-1α accumulation.HIF-1α protein played a critical role in TLR4-mediated lung injury of LIRI.HIF-1α up-regulated TLR4 expression in LIRI in a positive feedback manner.Conclusion We identify that HIF-1α has a damaging effect on TLR4 signaling pathway-mediated LIRI and TLR4-HIF-1 may synergistically involved in the development of LIRI.Therefore we suggest that the interaction between them may represent a novel therapeutic target for the development of novel target-based therapies of LIRI.
