WISP1 mediates hepatic warm ischemia reperfusion injury via TLR4 signaling in mice.
WISP1 mediates hepatic warm ischemia reperfusion injury via TLR4 signaling in mice.
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WISP1通过TLR4信号介导小鼠肝脏热缺血再灌注损伤
DOI：
10.1038/srep20141
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发表时间：
2016-01-29
影响因子：
4.6
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Tong Y;Ding XB;Chen ZX;Jin SQ;Zhao X;Wang X;Mei SY;Jiang X;Wang L;Li Q
wnt诱导分泌蛋白-1 （WISP1）是一种细胞外基质蛋白，在癌症研究中有报道。我们之前对WISP1的研究表明它可能是脓毒症小鼠的有害介质。然而，其在肝脏缺血再灌注（I/R）损伤中的作用尚不清楚。本研究探讨了WISP1对肝脏I/R损伤的影响。雄性C57BL/6野生型小鼠进行60 min（70%）节段性缺血。在指定时间点再灌注后检测WISP1的表达。小鼠腹腔注射抗wisp1抗体。本研究采用toll样受体4 （TLR4）敲除小鼠和含tir结构域适配器诱导干扰素-β (TRIF)敲除小鼠。与假手术小鼠相比，再灌注6 h后WISP1显著增强，TLR4敲除小鼠和TRIF敲除小鼠均显著降低。抗wisp1抗体显著降低I/R后小鼠血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、病理变化及促炎性细胞因子水平。此外，重组WISP1蛋白处理的C57野生型小鼠血清转氨酶水平显著升高，而TLR4敲除或TRIF敲除小鼠经肝I/R处理后血清转氨酶水平未见升高。综上所述，WISP1可能参与小鼠肝脏缺血再灌注损伤，并可能依赖于TLR4/TRIF信号。
Wnt-induced secreted protein-1 (WISP1) is an extracellular matrix protein that has been reported in cancer researches. Our previous studies on WISP1 implied it could be a harmful mediator in septic mice. However, its role in liver ischemia reperfusion (I/R) injury is unknown. This study investigated the effects of WISP1 on liver I/R damage. Male C57BL/6 wild-type mice were used to undergo 60 min segmental (70%) ischemia. WISP1 expression was measured after indicated time points of reperfusion. Anti-WISP1 antibody was injected intraperitoneally to mice. Toll-like receptor 4 (TLR4) knockout mice and TIR-domain-containing adaptor inducing interferon-β (TRIF) knockout mice were adopted in this study. WISP1 was significantly enhanced after 6 h of reperfusion when compared with sham treated mice and significantly decreased either by TLR4 knockout mice or TRIF knockout mice. Anti-WISP1 antibody significantly decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), pathological changes and pro-inflammatory cytokine levels in the mice following I/R. Furthermore, significantly increased serum transaminase levels were found in C57 wild-type mice treated with recombinant WISP1 protein, but not found in TLR4 knockout or TRIF knockout mice subjected to liver I/R. Taken together, WISP1 might contribute to hepatic ischemia reperfusion injury in mice and possibly depends on TLR4/TRIF signaling.