JG cell expression and partial regulation of a human renin genomic transgene driven by a minimal renin promoter.
In the kidney, renin gene expression is exquisitely localized to the juxtaglomerular (JG) cells lining the afferent arteriole, having the capacity to regulate renin synthesis in response to a variety of physiological cues. We investigated human renin gene expression in transgenic mice containing a genomic construct driven by 149 bp of its proximal promoter to elucidate whether this was sufficient to confer JG-specific expression. Whereas human renin mRNA was permissively expressed in most tissues, the transgene was expressed mainly in JG cells in the kidney. Active human renin and human prorenin were found in the systemic circulation at levels consistent with previous transgenic models. Remarkably, two lines displayed an appropriate upregulation of transgene mRNA in response to angiotensin-converting enzyme inhibition, and two lines exhibited a downregulation of transgene mRNA in response to subpressor and pressor doses of ANG II. Our results suggest that 149 bp of the human renin proximal promoter, in a context of a genomic construct, are sufficient to confer human renin expression in renal JG cells and at least some aspects of appropriate regulation.
Sinn
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Department of Internal Medicine, The University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
Zhang
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Sigmund
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D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015536:Down-Regulation; D005786:Gene Expression Regulation; D016678:Genome; D006801:Humans; D007606:Juxtaglomerular Apparatus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D012083:Renin / Q000235:genetics*; D019076:Transgenes / Q000235:genetics*; D015854:Up-Regulation
D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D000804:Angiotensin II; D012083:Renin