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Ouabain rescues rat nephrogenesis during intrauterine growth restriction by regulating the complement and coagulation cascades and calcium signaling pathway

Published online by Cambridge University Press:  07 October 2015

L. Chen ,
J. Yue ,
X. Han ,
J. Li  and
Y. Hu
L. Chen*
Affiliation:
Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
J. Yue
Affiliation:
Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
X. Han
Affiliation:
Department of Endocrinology, Yancheng Hospital of Traditional Chinese Medicine affiliated to Nanjing University of Chinese Medicine, Yancheng, China
J. Li
Affiliation:
Department of Hematology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
Y. Hu
Affiliation:
Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
*
*Address for correspondence: L. Chen, Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210009, Jiangsu Province, People’s Republic of China. (Email chenliang_nj@163.com)
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Abstract

Intrauterine growth restriction (IUGR) is associated with a reduction in the numbers of nephrons in neonates, which increases the risk of hypertension. Our previous study showed that ouabain protects the development of the embryonic kidney during IUGR. To explore this molecular mechanism, IUGR rats were induced by protein and calorie restriction throughout pregnancy, and ouabain was delivered using a mini osmotic pump. RNA sequencing technology was used to identify the differentially expressed genes (DEGs) of the embryonic kidneys. DEGs were submitted to the Database for Annotation and Visualization and Integrated Discovery, and gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. Maternal malnutrition significantly reduced fetal weight, but ouabain treatment had no significant effect on body weight. A total of 322 (177 upregulated and 145 downregulated) DEGs were detected between control and the IUGR group. Meanwhile, 318 DEGs were found to be differentially expressed (180 increased and 138 decreased) between the IUGR group and the ouabain-treated group. KEGG pathway analysis indicated that maternal undernutrition mainly disrupts the complement and coagulation cascades and the calcium signaling pathway, which could be protected by ouabain treatment. Taken together, these two biological pathways may play an important role in nephrogenesis, indicating potential novel therapeutic targets against the unfavorable effects of IUGR.

Keywords

calcium signaling pathwaycomplement and coagulation cascadesintrauterine growth restrictionnephrogenesisouabain
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 7 , Issue 1: Themed Issue: The Gut Microbiome and Immunity: How it is Shaped by Early Life , February 2016 , pp. 91 - 101
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2015 

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