Prenatal exposure to hypoxia induced Beclin 1 signaling-mediated renal autophagy and altered renal development in rat fetuses

产前暴露于缺氧会诱导 Beclin 1 信号介导的肾脏自噬并改变大鼠胎儿的肾脏发育

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作者:Shuixiu Xia, Juanxiu Lv, Qinqin Gao, Lingjun Li, Ningjing Chen, Xiaoguang Wei, Jianping Xiao, Jie Chen, Jianying Tao, Miao Sun, Caiping Mao, Lubo Zhang, Zhice Xu

Aims

Hypoxia has adverse effects on renal development. This study was the first to test hypoxia-induced renal autophagy in rat fetuses.

Conclusion

Hypoxia-affected fetal renal development was associated with renal apoptosis and Beclin 1 signaling-mediated autophagy.

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.

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