产前低氧诱导 Beclin 1 信号介导的肾自噬及改变胎鼠肾脏发育
Prenatal exposure to hypoxia induced Beclin 1 signaling-mediated renal autophagy and altered renal development in rat fetuses.
机构信息
Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
Institute for Fetology, First Hospital of Soochow University, Suzhou, China Center for Perinatal Biology, Loma Linda University, Loma Linda, CA, USA.
出版信息
Reprod Sci. 2015 Feb;22(2):156-64. doi: 10.1177/1933719114536474. Epub 2014 May 28.
AIMS
Hypoxia has adverse effects on renal development. This study was the first to test hypoxia-induced renal autophagy in rat fetuses.
METHODS
Pregnant rats were exposed to hypoxia or normoxia during pregnancy and fetal kidneys were collected at gestation day 21.
RESULTS
Fetal kidney weight and ratio of kidney-body weight were reduced. Histological analysis showed enlargement in Bowman space and wider space between interstitia in the kidneys of fetus exposed to hypoxia. Fetal renal B-cell lymphoma 2 (BCL-2) was decreased accompanied with higher 2'-deoxyuridine 5'-triphosphate nick end-labeling staining and unchanged soluble FAS in the hypoxia group. Hypoxia increased autophagic structures, including autophagosomes and autolysosomes, in fetal kidneys and increased renal APG5L. There was an increase in renal LC3-II, Beclin 1, p-S6, hypoxia inducible factor 1α (HIF-1a), and ratio of LC3-II-LC3-I and a decrease in P62, protein kinase B (AKT), and phosphorylated AKT in the hypoxia group. Both renal mammalian target of rapamycin (mTOR) and Beclin 1 signaling were upregulated.
CONCLUSION
Hypoxia-affected fetal renal development was associated with renal apoptosis and Beclin 1 signaling-mediated autophagy.
目的
缺氧对肾脏发育有不良影响。本研究首次测试了缺氧诱导的胎鼠肾脏自噬。
方法
在妊娠期间，将怀孕的大鼠暴露于缺氧或常氧环境中，并在妊娠第 21 天收集胎儿肾脏。
结果
胎儿肾脏重量和肾体比降低。组织学分析显示，在缺氧暴露的胎儿肾脏中，Bowman 空间增大，间质之间的空间变宽。胎儿肾 B 细胞淋巴瘤 2（BCL-2）减少，同时 2'-脱氧尿苷 5'-三磷酸末端标记染色增加，而缺氧组中可溶性 FAS 不变。缺氧增加了胎儿肾脏中的自噬结构，包括自噬体和自噬溶酶体，并增加了 APG5L。在缺氧组中，肾脏 LC3-II、Beclin 1、p-S6、缺氧诱导因子 1α（HIF-1α）和 LC3-II-LC3-I 比值增加，而 P62、蛋白激酶 B（AKT）和磷酸化 AKT 减少。肾哺乳动物雷帕霉素靶蛋白（mTOR）和 Beclin 1 信号通路均上调。
结论
缺氧影响胎儿肾脏发育与肾脏细胞凋亡和 Beclin 1 信号通路介导的自噬有关。
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