Toll-like receptor 4 regulates early endothelial activation during ischemic acute kidney injury.
Toll-like receptor 4 regulates early endothelial activation during ischemic acute kidney injury.
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DOI：
10.1038/ki.2010.381
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发表时间：
2011-02
影响因子：
19.6
通讯作者：
Lu, Christopher Y.
中科院分区：
文献类型：
--
作者：
Chen, Jianlin;John, Reji;Richardson, James A.;Shelton, John M.;Zhou, Xin J.;Wang, Yanxia;Wu, Qing Qing;Hartono, John R.;Winterberg, Pamela D.;Lu, Christopher Y.
缺血性急性肾损伤 (AKI) 会引发炎症反应，从而加剧损伤，从而需要增加内皮粘附分子的表达。为了进一步研究这一点，我们采用原位杂交、免疫组织学和分离的内皮细胞，发现再灌注4小时后，肾脏外髓质内条纹的直肠血管内皮细胞上Toll样受体4（TLR4）表达增加。这种增加可能是由于已知在缺血性 AKI 早期产生的活性氧所致，因为添加过氧化氢会增加体外 MS1 微血管内皮细胞中 TLR4 的表达。内皮 TLR4 可能调节粘附分子（CD54 和 CD62E）的表达，因为它们在野生型小鼠的内皮细胞上增加，但体内 TLR4 敲除小鼠的内皮细胞上却没有增加。此外，添加高迁移率组蛋白 B1（一种由受损细胞释放的 TLR4 配体）可增加从野生型而非 TLR4 敲除小鼠中分离的内皮细胞上粘附分子的表达。再灌注 24 小时后，TLR4 定位于皮质和外髓质的近端小管。因此，至少有两种不同的细胞类型表达 TLR4，每种细胞在缺血性 AKI 期间通过暂时不同的机制导致肾损伤。
Ischemic acute kidney injury (AKI) triggers an inflammatory response which exacerbates injury that requires increased expression of endothelial adhesion molecules. To study this further, we used in situ hybridization, immunohistology, and isolated endothelial cells, and found increased Toll-like receptor 4 (TLR4) expression on endothelial cells of the vasa rectae of the inner stripe of the outer medulla of the kidney 4 h after reperfusion. This increase was probably due to reactive oxygen species, known to be generated early during ischemic AKI, because the addition of hydrogen peroxide increased TLR4 expression in MS1 microvascular endothelial cells in vitro. Endothelial TLR4 may regulate adhesion molecule (CD54 and CD62E) expression as they were increased on endothelia of wild-type but not TLR4 knockout mice in vivo. Further, the addition of high-mobility group protein B1, a TLR4 ligand released by injured cells, increased adhesion molecule expression on endothelia isolated from wild-type but not TLR4 knockout mice. TLR4 was localized to proximal tubules in the cortex and outer medulla after 24 h of reperfusion. Thus, at least two different cell types express TLR4, each of which contributes to renal injury by temporally different mechanisms during ischemic AKI.
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DOI：
10.1159/000142934
发表时间：
2008
期刊：
Nephron. Experimental nephrology
影响因子：
--
作者：
Kinsey GR;Li L;Okusa MD
通讯作者：
Okusa MD
影响因子：
8.6
作者：
Jang, Hye Ryoun;Rabb, Hamid
通讯作者：
Rabb, Hamid
影响因子：
4.8
作者：
Arany, Istvan;Faisal, Amir;Safirstein, Robert L.
通讯作者：
Safirstein, Robert L.
影响因子：
19.6
作者：
Bonventre, JV;Zuk, A
通讯作者：
Zuk, A
影响因子：
3.2
作者：
Laitinen, Liisa;Virtanen, Ismo;Saxen, Lauri
通讯作者：
Saxen, Lauri