Dynamic expression and roles of sequestome‑1/p62 in LPS‑induced acute kidney injury in mice.
Dynamic expression and roles of sequestome‑1/p62 in LPS‑induced acute kidney injury in mice.
复制标题
Sequestome-1/p62 在 LPS- 诱导的小鼠急性肾损伤中的动态表达和作用
DOI：
10.3892/mmr.2018.8809
复制
发表时间：
2018-06
影响因子：
3.4
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Li T;Zhao J;Miao S;Xu Y;Xiao X;Liu Y
急性肾损伤(AKI)是败血症最常见的并发症之一。自噬在AKI中的作用已经在以前的研究中得到了证明。Sequestosome-1(P62)已被证明在自噬中起重要作用。自噬的失调会导致p62的积聚，这与炎症和肿瘤的增加有关。然而，p62在败血症AKI中的表达模式和作用仍不清楚。本研究检测了脂多糖(LPS)诱导的AKI小鼠模型中肾脏的自噬水平，以及p62的表达和定位。结果表明，内毒素可诱导小鼠肾脏自噬。脂多糖处理组小鼠全肾组织中p62mRNA和蛋白表达水平降低，而蛋白表达水平升高。免疫组织化学结果显示，正常情况下，p62蛋白主要表达在近曲小管的胞浆中，而注射内毒素后，p62蛋白表达明显减少。此外，在脂多糖处理后，p62蛋白逐渐重新分布到外、内髓。体外实验表明，p62过表达显著降低了肾小管上皮细胞的存活率，增加了乳酸脱氢酶(LDH)的释放，增加了细胞凋亡率。相反，使用小干扰RNA干扰p62的表达可提高细胞存活率，减少乳酸脱氢酶的释放，降低细胞凋亡率。本研究结果表明，p62可能通过促进肾小管上皮细胞的凋亡而加重脂多糖诱导的小鼠急性肾损伤。
Acute kidney injury (AKI) is one of the most common complications of sepsis. The roles of autophagy in AKI have been demonstrated in previous studies. Sequestosome-1 (p62) has been demonstrated to serve essential roles in autophagy. The dysregulation of autophagy causes p62 accumulation, which is associated with increased inflammation and tumorigenesis. However, the expression patterns and role of p62 in septic AKI remain unknown. The present study detected the renal autophagy level, and the expression and localization of p62, in a lipopolysaccharide (LPS)-induced AKI mouse model. The results demonstrated that autophagy was induced in the kidneys of LPS-treated mice. The mRNA and protein levels of p62 were decreased in whole renal tissue samples and increased in mice treated with LPS. Immunohistochemistry indicated that p62 protein was predominantly expressed in the cytoplasm of proximal tubules under normal conditions and was significantly decreased following LPS injection into the cortex. In addition, p62 protein was gradually redistributed to the outer and inner medullas following treatment with LPS. In vitro experiments demonstrated that overexpression of p62 significantly decreased the viability and increased the lactate dehydrogenase (LDH) release and apoptosis rate, of renal tubular epithelial cells. By contrast, interference with p62 expression using small interfering RNA increased the cell viability and decreased the LDH release and apoptosis rate. The results of the present study demonstrated that p62 may aggravate LPS-induced acute kidney injury in mice by promoting apoptosis in renal tubular epithelial cells.
登录
查看更多内容
自噬限制内毒素急性肾损伤，并改变肾小管上皮细胞因子表达。
影响因子：
3.7
作者：
Leventhal JS;Ni J;Osmond M;Lee K;Gusella GL;Salem F;Ross MJ
通讯作者：
Ross MJ
影响因子：
--
作者：
Lippai M;Lőw P
通讯作者：
Lőw P
影响因子：
4.8
作者：
Han, Jie;Hou, Wen;Rabinowich, Hannah
通讯作者：
Rabinowich, Hannah
影响因子：
64.5
作者：
Jin, Zhaoyu;Li, Yun;Ashkenazi, Avi
通讯作者：
Ashkenazi, Avi
DOI：
10.1152/ajprenal.00512.2013
发表时间：
2014-08-15
影响因子：
4.2
作者：
Liu, Ying;Jia, Zhanjun;Yang, Tianxin
通讯作者：
Yang, Tianxin