| Genetic low nephron number hypertension is associated with dysregulation of the hepatic and renal insulin-like growth factor system during nephrogenesis. | |
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MedLine Citation:
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PMID: 16915036 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Low nephron number may represent a major determinant of human primary hypertension in adult life. This hypothesis is supported by a genetic rat model, namely the Munich-Wistar-Frömter (MWF) rat, which demonstrates an inherited deficit in nephron number and the development of spontaneous hypertension. Insulin-like growth factor (IGF) I and II exert endocrine and paracrine effects that are required for normal growth and nephron development. We tested the hypothesis that low nephron number is already present during fetal development, and the expression pattern of important molecules of the IGF system is altered in MWF rat during the critical period of kidney development. METHODS: We compared MWF and normal Wistar rats during nephrogenesis at day 19 of fetal development (E19) and adult rats at postnatal day 100 (D100). Histomorphometric analysis was performed by stereological methods. Quantitative messenger RNA and protein expression was determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: At E19, glomerular density (-32%) and hepatic mRNA (-48%) and protein (-18%) expression of IGF-I were decreased (P < 0.05, respectively), whereas renal mRNA expression of IGF-II receptor (+52%) and IGF binding protein 3 (+113%) were increased in MWF compared with Wistar rats (P < 0.05, respectively). Systolic blood pressure, urinary albumin excretion, and mean glomerular area were significantly elevated in MWF compared with Wistar rats at D100 (P < 0.05, respectively). CONCLUSIONS: The fetal expression of IGF system molecules in the MWF rat model points towards a link between the decreased availability of active IGF-I and IGF-II and the fetal development of low nephron number, with manifestation of genetic hypertension in adult life. |
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Authors:
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Lars Rothermund; Marc Nierhaus; Olaf Fialkowski; Florian Freese; Ricarda Ibscher; Susanne Mieschel; Peter Kossmehl; Daniela Grimm; Markus Wehland; Reinhold Kreutz |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of hypertension Volume: 24 ISSN: 0263-6352 ISO Abbreviation: J. Hypertens. Publication Date: 2006 Sep |
Date Detail:
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Created Date: 2006-08-17 Completed Date: 2007-01-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8306882 Medline TA: J Hypertens Country: England |
Other Details:
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Languages: eng Pagination: 1857-64 Citation Subset: IM |
Affiliation:
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Medizinische Klinik IV, Endokrinologie und Nephrologie, Charité Universitätsmedizin Berlin, Berlin, Germany. lars.rothermund@charite.de |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Body Weight Enzyme-Linked Immunosorbent Assay Gene Expression Regulation* Hormones / metabolism Hypertension / etiology*, genetics*, physiopathology Kidney / metabolism*, pathology Kidney Glomerulus / metabolism Liver / metabolism* Male Nephrons / metabolism, pathology* RNA, Messenger / metabolism Rats Rats, Wistar Somatomedins / biosynthesis, physiology* |
| Chemical | |
Reg. No./Substance:
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0/Hormones; 0/RNA, Messenger; 0/Somatomedins |
| Comments/Corrections | |
Comment In:
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J Hypertens. 2006 Sep;24(9):1707-9
[PMID:
16915017
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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