Shuixiu Xia1, Juanxiu Lv1, Qinqin Gao1, Lingjun Li1, Ningjing Chen1, Xiaoguang Wei1, Jianping Xiao1, Jie Chen1, Jianying Tao1, Miao Sun1, Caiping Mao1, Lubo Zhang2, Zhice Xu3. 1. Institute for Fetology, First Hospital of Soochow University, Suzhou, China. 2. Institute for Fetology, First Hospital of Soochow University, Suzhou, China Center for Perinatal Biology, Loma Linda University, Loma Linda, CA, USA. 3. Institute for Fetology, First Hospital of Soochow University, Suzhou, China Center for Perinatal Biology, Loma Linda University, Loma Linda, CA, USA xuzhice@suda.edu.cn.
Abstract
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.
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.
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