Mice with an absent stress response are protected against ischemic renal injury.
Mice with an absent stress response are protected against ischemic renal injury.
复制标题
缺乏应激反应的小鼠可以免受缺血性肾损伤。
DOI：
10.1038/ki.2014.73
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发表时间：
2014
影响因子：
19.6
通讯作者：
VanWhy,ScottK
中科院分区：
文献类型：
--
作者：
Sreedharan,Rajasree;Chen,Shaoying;Miller,Melody;Haribhai,Dipica;Williams,CalvinB;VanWhy,ScottK
诱导型热休克蛋白（Inducible heat shock proteins，HSPs）受热休克因子-1（heat shock factor-1，HSF-1）的调节，在体外对肾细胞损伤具有保护作用。为了确定热休克蛋白是否能改善体内缺血性肾损伤，将HSF-1功能敲除小鼠（HSF-KO）与野生型小鼠在双侧缺血性肾损伤后进行比较。损伤后，野生型小鼠的肾脏具有预期的HSP 70和HSP 25诱导; HSF-KO小鼠的肾脏中不存在这种反应。两种菌株之间的基线血清肌酐相当。HSF-KO小鼠在24小时再流时的血清肌酐显著低于野生型。组织学显示，缺血性肾损伤后，两种品系的肾小管损伤相似，但与HSF-KO小鼠相比，野生型小鼠的髓质血管充血增加。从肾脏分离的单核细胞的流式细胞术显示假手术动物中的CD 4+和CD 8 +T细胞的数量在菌株之间没有差异。在1小时的复流，CD 4+和CD 8+细胞在野生型但不是HSF-KO小鼠的肾脏加倍。Foxp 3 + T调节细胞在假手术HSF-KO小鼠的肾脏中比野生型小鼠显著更丰富。用抗CD 25抗体PC61抑制HSF-KO肾中的CD 25 + Foxp 3+细胞逆转了针对缺血性肾损伤的保护。因此，HSF-KO小鼠通过依赖于与回流早期改变的T细胞浸润相关的肾脏中T调节细胞的增加的机制而免受缺血性肾损伤。因此，应激反应激活可能通过促进T细胞浸润到缺血肾脏而促进早期损伤。
Inducible heat shock proteins (HSPs), regulated by heat shock factor-1 (HSF-1), protect against renal cell injuryin vitro. To determine whether HSPs ameliorate ischemic renal injuryin vivo, HSF-1 functional knockout mice (HSF-KO) were compared with wild-type mice following bilateral ischemic renal injury. Following injury, the kidneys of wild-type mice had the expected induction of HSP70 and HSP25; a response absent in the kidneys of HSF-KO mice. Baseline serum creatinine was equivalent between strains. Serum creatinine at 24 h reflow in HSF-KO mice was significantly lower than that in the wild type. Histology showed similar tubule injury in both strains after ischemic renal injury but increased medullary vascular congestion in wild-type compared with HSF-KO mice. Flow cytometry of mononuclear cells isolated from kidneys showed no difference between strains in the number of CD4+and CD8+T cells in sham-operated animals. At 1 h of reflow, CD4+and CD8+cells were doubled in the kidneys of wild-type but not HSF-KO mice. Foxp3+T-regulatory cells were significantly more abundant in the kidneys of sham-operated HSF-KO than wild-type mice. Suppression of CD25+Foxp3+cells in HSF-KO kidneys with the anti-CD25 antibody PC61 reversed the protection against ischemic renal injury. Thus, HSF-KO mice are protected from ischemic renal injury by a mechanism that depends on an increase in the T-regulatory cells in the kidney associated with altered T-cell infiltration early in reflow. Hence, stress response activation may contribute to early injury by facilitating T-cell infiltration into ischemic kidney.