What Have We Learned from Gene Targeting Studies for the Renin Angiotensin System of the Kidney?

Nishimura, Hideki; Ichikawa, Iekuni

doi:10.2169/internalmedicine.38.315

Cited by 16 publications

(13 citation statements)

References 59 publications

(45 reference statements)

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“…The direct actions of angiotensin II in the kidney include an increase in tubular sodium reabsorption and an influence on glomerular filtration rate (GFR), but morphopathological changes such as accumulation of extracellular matrix and mesangial cell proliferation and hypertrophy 17,18 are of more importance for the pathogenesis of renal impairment. Therefore, the question has arisen as to whether pharmacological intervention in the RAS confers an additional benefit beyond the lowering of blood pressure.…”

Section: Discussionmentioning

confidence: 99%

Interim evidence of the renoprotective effect of the angiotensin II receptor antagonist losartan versus the calcium channel blocker amlodipine in patients with chronic kidney disease and hypertension: a report of the Japanese Losartan Therapy Intended for Global Renal Protection in Hypertensive Patients (JLIGHT) Study

Iino

Hayashi

Kawamura

et al. 2003

Clinical and Experimental Nephrology

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Section: Discussionmentioning

confidence: 99%

Interim evidence of the renoprotective effect of the angiotensin II receptor antagonist losartan versus the calcium channel blocker amlodipine in patients with chronic kidney disease and hypertension: a report of the Japanese Losartan Therapy Intended for Global Renal Protection in Hypertensive Patients (JLIGHT) Study

Iino

Hayashi

Kawamura

et al. 2003

Clinical and Experimental Nephrology

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“…More recently, it has become evident that a functional RAS is required for normal mammalian renal development. 1 Renin, an aspartyl protease, initiates an enzymatic cascade that results in the production of the vasoactive peptide angiotensin II, the major effector molecule of the RAS. Transcription of renin genes is tissuespecifically and developmentally regulated.…”

mentioning

confidence: 99%

Transcriptional Regulation of Renin

Gross

2005

Hypertension

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Abstract-Renin, as a component of the renin-angiotensin system, plays important roles in the regulation of blood pressure, electrolyte homeostasis, and mammalian renal development. Transcription of renin genes is subject to complex developmental and tissue-specific regulation. Progress has been made recently in elucidating the molecular mechanisms involved in renin gene expression. Using mouse As4.1 cells, which have many features characteristic of the renin-expressing juxtaglomerular cells of kidney, a proximal promoter region (Ϫ197 to Ϫ50 bp) and an enhancer (Ϫ2866 to Ϫ2625 bp) have been identified in the mouse renin gene, Ren-1 c , that are critical for its expression. The proximal promoter region contains at least 7 transcription factor-binding sites, including a binding site for the products of Hox, developmental control genes. The enhancer consists of at least 11 transcription factor-binding sites and is responsive to various signal transduction pathways, including cAMP, retinoic acid, endothelin-1, and cytokines, to alter renin mRNA levels. Sequence highly homologous to the mouse enhancer is also found in the human and rat renin genes. How these regulatory regions function in vivo will be the focus of future study. Key Words: renin Ⅲ transcription T he renin-angiotension system (RAS) has long been recognized to play a critical role in blood pressure homeostasis and electrolyte balance. More recently, it has become evident that a functional RAS is required for normal mammalian renal development. 1 Renin, an aspartyl protease, initiates an enzymatic cascade that results in the production of the vasoactive peptide angiotensin II, the major effector molecule of the RAS. Transcription of renin genes is tissuespecifically and developmentally regulated. 2 The principle source of active renin in the circulation is the kidney. In the mouse kidney, renin expression is first detected at 14.5 days of gestation in the earliest developing arteries, and is then found in the newly forming arterial branches as the renal arterial tree develops. Subsequently, renin expression is progressively restricted to smaller arteries and arterioles until, in the adult, it is abundantly expressed in juxtaglomerular cells located in the wall of the afferent arteriole. A number of other tissues also express renin genes in mice, including submandibular gland, adrenal gland, testes, ovary, anterior prostate, brain, and fetal subcutaneous tissue.Results from transgenic studies have shown that Ϸ4 kb of the mouse renin 5Ј flanking sequence is sufficient to specify correct renin expression patterns in mouse embryonic, extraembryonic, and adult tissues using SV40 T antigen or GFP as reporters, suggesting that the most important regulatory regions reside within this region. 3,4 Availability of these transgenic lines has allowed us to isolate a renin-expressing kidney tumor cell line (As4.1) 5 and apply fluorescence-activated cell sorting (FACS) to acquire natural renin-expressing cells, valuable for identifying cis-acting elements and transactin...

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“…Additionally, the reninangiotensin system has been implicated in aspects of renal development by the observation that pharmacological and genetic disruptions of renin-angiotensin system function result in aberrant renal morphology (for reviews, see Refs. [2][3][4].…”

mentioning

confidence: 99%

“…The PPE was shown to bind As4.1 cell nuclear proteins in electrophoretic mobility shift assays (EMSAs). Further competition assays indicated that the minimal sequence required for protein binding included N (1)(2)(3) TAATAAATCA. Mutation of the PPE in the Ren-CAT construct containing a 4.1-kb mouse renin sequence dramatically reduced the chloramphenicol acetyltransferase activity in transfection assays suggesting a critical role of this element in the regulation of mouse renin gene expression.…”

mentioning

confidence: 99%

An Abd-B Class HOX·PBX Recognition Sequence Is Required for Expression from the Mouse Ren-1 Gene

Xie

Black

et al. 2001

Journal of Biological Chemistry

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What Have We Learned from Gene Targeting Studies for the Renin Angiotensin System of the Kidney?

Cited by 16 publications

References 59 publications

Transcriptional Regulation of Renin

An Abd-B Class HOX·PBX Recognition Sequence Is Required for Expression from the Mouse Ren-1 Gene

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