Renal HIV expression is unaffected by serum LPS levels in an HIV transgenic mouse model of LPS induced kidney injury.
Renal HIV expression is unaffected by serum LPS levels in an HIV transgenic mouse model of LPS induced kidney injury.
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DOI：
10.1371/journal.pone.0020688
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Ross MJ
中科院分区：
文献类型：
--
作者：
Leventhal JS;Alsauskas Z;Snyder A;Gong P;Wang B;D'Agati V;Ross MJ
急性肾损伤（阿基）与死亡率增加有关。由于未知的原因，HIV感染者比未感染者有更高的阿基风险。我们验证了我们的假设，即循环LPS增加会增加HIV的肾脏表达，HIV转基因（Tg 26）小鼠对阿基的易感性增加。Tg 26小鼠携带编码除gag和pol之外的所有HIV基因的HIV转基因，并产生类似于HIVAN的表型。在出现肉眼可见的肾脏疾病之前，使用4-6周龄的小鼠。用LPS或无菌盐水腹膜内注射小鼠。在Tg 26和野生型（WT）小鼠中评估了肾功能、肾小管损伤、细胞因子表达和HIV转录。LPS注射诱导脾脏中HIV表达增加60.1倍，但肾脏中无变化。在基线或LPS注射后24小时，肾功能、细胞因子表达或肾小管损伤评分无显著差异。还使用人肾小管上皮细胞（RTEC）系在体外分析HIV转录。在LPS暴露后48小时，HIV转录在人RTEC中最低限度地增加1.47倍。我们得出结论，Tg 26小鼠不增加HIV表达或增加对LPS诱导的阿基的易感性。HIV感染患者中阿基风险增加并非通过脓毒症背景下HIV肾表达增加介导。此外，肾脏对HIV转录的调节与脾脏不同。
Acute kidney injury (AKI) is associated with increased rates of mortality. For unknown reasons, HIV infected individuals have a higher risk of AKI than uninfected persons. We tested our hypothesis that increased circulating LPS increases renal expression of HIV and that HIV transgenic (Tg26) mice have increased susceptibility to AKI. Tg26 mice harbor an HIV transgene encoding all HIV genes except gag and pol, and develop a phenotype analogous to HIVAN. Mice were used at 4–6 weeks of age before the onset of gross renal disease. Mice were injected i.p. with LPS or sterile saline. Renal function, tubular injury, cytokine expression, and HIV transcription were evaluated in Tg26 and wild type (WT) mice. LPS injection induced a median 60.1-fold increase in HIV expression in spleen but no change in kidney. There was no significant difference in renal function, cytokine expression, or tubular injury scores at baseline or 24 hours after LPS injection. HIV transcription was also analyzed in vitro using a human renal tubular epithelial cell (RTEC) line. HIV transcription increased minimally in human RTEC, by 1.47 fold, 48 hours after LPS exposure. We conclude that Tg26 mice do not increase HIV expression or have increased susceptibility to LPS induced AKI. The increased risk of AKI in HIV infected patients is not mediated via increased renal expression of HIV in the setting of sepsis. Moreover, renal regulation of HIV transcription is different to that in the spleen.
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