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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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References

1. Peyter, AC, Delhaes, F, Baud, D, et al. Intrauterine growth restriction is associated with structural alterations in human umbilical cord and decreased nitric oxide-induced relaxation of umbilical vein. Placenta. 2014; 35, 891–899.Google Scholar
2. Pisaneschi, S, Boldrini, A, Genazzani, AR, Coceani, F, Simoncini, T. Feto-placental vascular dysfunction as a prenatal determinant of adult cardiovascular disease. Intern Emerg Med. 2013; 8(Suppl. 1), S41–S45.Google Scholar
3. Bamfo, JE, Odibo, AO. Diagnosis and management of fetal growth restriction. J Pregnancy. 2011; 2011, 640715.Google Scholar
4. Myrie, SB, McKnight, LL, Van Vliet, BN, Bertolo, RF. Low birth weight is associated with reduced nephron number and increased blood pressure in adulthood in a novel spontaneous intrauterine growth-restricted model in Yucatan miniature swine. Neonatology. 2011; 100, 380–386.Google Scholar
5. Baserga, M, Bares, AL, Hale, MA, et al. Uteroplacental insufficiency affects kidney VEGF expression in a model of IUGR with compensatory glomerular hypertrophy and hypertension. Early Hum Dev. 2009; 85, 361–367.Google Scholar
6. Stuart, RO, Bush, KT, Nigam, SK. Changes in gene expression patterns in the ureteric bud and metanephric mesenchyme in models of kidney development. Kidney Int. 2003; 64, 1997–2008.Google Scholar
7. Figueroa, H, Lozano, M, Suazo, C, et al. Intrauterine growth restriction modifies the normal gene expression in kidney from rabbit fetuses. Early Hum Dev. 2012; 88, 899–904.Google Scholar
8. Baserga, M, Hale, MA, Wang, ZM, et al. Uteroplacental insufficiency alters nephrogenesis and downregulates cyclooxygenase-2 expression in a model of IUGR with adult-onset hypertension. Am J Physiol Regul Integr Comp Physiol. 2007; 292, R1943–R1955.CrossRefGoogle Scholar
9. Grigore, D, Ojeda, NB, Robertson, EB, et al. Placental insufficiency results in temporal alterations in the renin angiotensin system in male hypertensive growth restricted offspring. Am J Physiol Regul Integr Comp Physiol. 2007; 293, R804–R811.Google Scholar
10. Shah, JR, Laredo, J, Hamilton, BP, Hamlyn, JM. Different signaling pathways mediate stimulated secretions of endogenous ouabain and aldosterone from bovine adrenocortical cells. Hypertension. 1998; 31(Pt 2), 463–468.CrossRefGoogle ScholarPubMed
11. Murrell, JR, Randall, JD, Rosoff, J, et al. Endogenous ouabain: upregulation of steroidogenic genes in hypertensive hypothalamus but not adrenal. Circulation. 2005; 112, 1301–1308.Google Scholar
12. Lichtstein, D, Steinitz, M, Gati, I, et al. Biosynthesis of digitalis-like compounds in rat adrenal cells: hydroxycholesterol as possible precursor. Life Sci. 1998; 62, 2109–2126.Google Scholar
13. Dvela-Levitt, M, Cohen-Ben Ami, H, Rosen, H, et al. Reduction in maternal circulating ouabain impairs offspring growth and kidney development. J Am Soc Nephrol. 2015; 26, 1103–1114.Google Scholar
14. Liu, J, Xie, ZJ. The sodium pump and cardiotonic steroids-induced signal transduction protein kinases and calcium-signaling microdomain in regulation of transporter trafficking. Biochim Biophys Acta. 2010; 1802, 1237–1245.Google Scholar
15. Johansson, M, Karlsson, L, Wennergren, M, Jansson, T, Powell, TL. Activity and protein expression of Na+/K+ ATPase are reduced in microvillous syncytiotrophoblast plasma membranes isolated from pregnancies complicated by intrauterine growth restriction. J Clin Endocrinol Metab. 2003; 88, 2831–2837.CrossRefGoogle ScholarPubMed
16. Xie, Z, Askari, A. Na(+)/K(+)-ATPase as a signal transducer. Eur J Biochem. 2002; 269, 2434–2439.CrossRefGoogle Scholar
17. Xie, Z, Cai, T. Na+-K+-ATPase-mediated signal transduction: from protein interaction to cellular function. Mol Interv. 2003; 3, 157–168.Google Scholar
18. Li, J, Khodus, GR, Kruusmagi, M, et al. Ouabain protects against adverse developmental programming of the kidney. Nat Commun. 2010; 1, 42.CrossRefGoogle ScholarPubMed
19. Li, J, Zelenin, S, Aperia, A, Aizman, O. Low doses of ouabain protect from serum deprivation-triggered apoptosis and stimulate kidney cell proliferation via activation of NF-kappaB. J Am Soc Nephrol. 2006; 17, 1848–1857.Google Scholar
20. Khodus, GR, Kruusmagi, M, Li, J, Liu, XL, Aperia, A. Calcium signaling triggered by ouabain protects the embryonic kidney from adverse developmental programming. Pediatr Nephrol. 2011; 26, 1479–1482.Google Scholar
21. Chen, L, Yue, J, Wu, H, et al. Ouabain attenuates cardiac hypertrophy of male rat offspring exposed to intrauterine growth restriction following high-salt diet challenge. Reprod Sci. 2015 [E-pub ahead of print].Google Scholar
22. Stuart, RO, Bush, KT, Nigam, SK. Changes in global gene expression patterns during development and maturation of the rat kidney. Proc Natl Acad Sci USA. 2001; 98, 5649–5654.Google Scholar
23. Buffat, C, Boubred, F, Mondon, F, et al. Kidney gene expression analysis in a rat model of intrauterine growth restriction reveals massive alterations of coagulation genes. Endocrinology. 2007; 148, 5549–5557.Google Scholar
24. Connolly, BM, Choi, EY, Gardsvoll, H, et al. Selective abrogation of the uPA-uPAR interaction in vivo reveals a novel role in suppression of fibrin-associated inflammation. Blood. 2010; 116, 1593–1603.CrossRefGoogle ScholarPubMed
25. Hoehlig, K, Maasch, C, Shushakova, N, et al. A novel C5a-neutralizing mirror-image (l-)aptamer prevents organ failure and improves survival in experimental sepsis. Mol Ther. 2013; 21, 2236–2246.Google Scholar
26. Blom, AM, Bergmann, S, Fulde, M, Riesbeck, K, Agarwal, V. Streptococcus pneumoniae phosphoglycerate kinase is a novel complement inhibitor affecting the membrane attack complex formation. J Biol Chem. 2014; 289, 32499–32511.Google Scholar
27. Distelmaier, K, Adlbrecht, C, Jakowitsch, J, et al. Local complement activation triggers neutrophil recruitment to the site of thrombus formation in acute myocardial infarction. Thromb Haemost. 2009; 102, 564–572.Google Scholar
28. Chen, X, Luther, G, Zhang, W, et al. The E-F hand calcium-binding protein S100A4 regulates the proliferation, survival and differentiation potential of human osteosarcoma cells. Cell Physiol Biochem. 2013; 32, 1083–1096.Google Scholar
29. Hung, CJ, Hsu, HI, Lin, CC, et al. The role of integrin alphav in proliferation and differentiation of human dental pulp cell response to calcium silicate cement. J Endod. 2014; 40, 1802–1809.Google Scholar
30. Schwitzgebel, VM, Somm, E, Klee, P. Modeling intrauterine growth retardation in rodents: impact on pancreas development and glucose homeostasis. Mol Cell Endocrinol. 2009; 304, 78–83.Google Scholar
31. Mumbare, SS, Maindarkar, G, Darade, R, et al. Maternal risk factors associated with term low birth weight neonates: a matched-pair case control study. Indian Pediatr. 2012; 49, 25–28.Google Scholar
32. Michels, KB, Harris, HR, Barault, L. Birthweight, maternal weight trajectories and global DNA methylation of LINE-1 repetitive elements. PLoS One. 2011; 6, e25254.Google Scholar
33. Davis, RR, Hofferth, SL. The association between inadequate gestational weight gain and infant mortality among U.S. infants born in 2002. Matern Child Health J. 2012; 16, 119–124.CrossRefGoogle ScholarPubMed
34. Benziane, B, Bjornholm, M, Pirkmajer, S, et al. Activation of AMP-activated protein kinase stimulates Na+,K+-ATPase activity in skeletal muscle cells. J Biol Chem. 2012; 287, 23451–23463.Google Scholar
35. Rees, S, Kittikulsuth, W, Roos, K, et al. Adenylyl cyclase 6 deficiency ameliorates polycystic kidney disease. J Am Soc Nephrol. 2014; 25, 232–237.Google Scholar
36. Bates, CM. Role of fibroblast growth factor receptor signaling in kidney development. Am J Physiol Renal Physiol. 2011; 301, F245–F251.Google Scholar
37. Wilkinson, L, Gilbert, T, Kinna, G, et al. Crim1KST264/KST264 mice implicate Crim1 in the regulation of vascular endothelial growth factor-A activity during glomerular vascular development. J Am Soc Nephrol. 2007; 18, 1697–1708.Google Scholar
38. Nabais Sa, MJ, Storey, H, Flinter, F, et al. Collagen type IV-related nephropathies in Portugal: pathogenic COL4A3 and COL4A4 mutations and clinical characterization of 25 families. Clin Genet. 2014 [E-pub ahead of print].Google Scholar
39. Dvela, M, Rosen, H, Ben-Ami, HC, Lichtstein, D. Endogenous ouabain regulates cell viability. Am J Physiol Cell Physiol. 2012; 302, C442–C452.Google Scholar