Development of the kidney vasculature

Gomez, R. Ariel; Norwood, Victoria F.; Tufro-McReddie, Alda

doi:10.1002/(sici)1097-0029(19971101)39:3<254::aid-jemt5>3.0.co;2-k

Cited by 40 publications

(26 citation statements)

References 31 publications

(31 reference statements)

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“…It is interesting that 12(S)-HETE is an important mediator of the effects of angiotensin II on vascular structure and function in adults (14,34). Moreover, 12(S)-HETE seems to be critically involved in angiogenesis (35), a process that is needed for kidney vascularization (7). It is tempting to speculate that decreased expression of such a vasoactive substance during kidney development, as demonstrated by both microarray and Western immunoblot, may disturb renal vascular development.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the first aim of the present study was to use DNA microarray to identify genes involved in the RAS-mediated developmental process of renal medulla, a region where the predominant structural-functional defects are found in rats subjected to neonatal RAS inhibition. In developing renal medulla, the medullary rays and blood vessels have been shown to express AT 1 receptors (7,8). We used the AT 1 receptor antagonist losartan because we wanted to study expression of genes related specifically to the AT 1 receptor.…”

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confidence: 99%

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Neonatal Losartan Treatment Suppresses Renal Expression of Molecules Involved in Cell-Cell and Cell-Matrix Interactions

Chen¹,

Lasaitiene²,

Gabrielsson

et al. 2004

Journal of the American Society of Nephrology

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Abstract. Lack of neonatal angiotensin II type 1 receptor (AT 1 ) stimulation produces renal abnormalities characterized by papillary atrophy and impaired urinary concentrating ability, but the mechanisms involved are still unclear. DNA microarray was used to identify genes that are differentially expressed in renal medulla in response to neonatal treatment with AT 1 receptor antagonist losartan (30 mg/kg per d), which commenced within 24 h after birth. The data showed that losartan treatment for 48 h downregulated 68 genes,~30% of which encode various components of cytoskeleton and cytoskeletonassociated proteins, extracellular matrix, and enzymes involved in extracellular matrix maturation or turnover. With the use of immunohistochemistry and Western immunoblot, the microarray data were confirmed and it was demonstrated that losartan suppressed renal expression of syndecan 2, ␣-smooth muscle actin, MHC class II, and leukocyte type 12-lipoxygenase by day 4. In addition, losartan inhibited medullary expression of integrin ␣6 and caused relocalization of integrins ␣6 and ␣3. Moreover, losartan inhibited cell proliferation in medullary tubules by day 9, as detected by Ki-67 immunostaining. This study provides new data supporting the contention that a lack of AT 1 receptor stimulation results in abnormal matrix assembly, disturbed cell-cell and cell-matrix interactions, and subsequent abnormal tubular maturation. Moreover, regulation of the expression of leukocyte type 12-lipoxygenase and ␣-smooth muscle actin by the renin-angiotensin system in the immature kidney adds new knowledge toward the understanding of renal vascular development.Renal maldevelopment in premature infants and infants who are small for gestational age is known to be related to hypertension in adult life (1) and may be attributed to the suppressed intrarenal renin-angiotensin system (RAS) in neonates (2). In humans, nephrogenesis is completed before gestational week 36, whereas, in rodents, nephrogenesis is not completed until 10 d after birth (3). Thus, rats and mice are born with immature kidneys, and the first 2 postnatal weeks correspond approximately to the second and third trimesters in humans. This difference provides a convenient animal model for studying mechanisms underlying the RAS-mediated kidney development in human fetus.The importance of the RAS for normal kidney development has been demonstrated by a number of studies using gene targeting or pharmacologic interruption of the RAS (4). Thus, inhibition of angiotensin-converting enzyme activity or angiotensin II type 1 receptor (AT 1 ) but not AT 2 signaling in animals with an ongoing nephrogenesis induces kidney abnormalities (5). The most pronounced structural change is papillary atrophy, and it is associated with impaired urinary concentrating ability (5). Kidney vasculature is also affected, characterized by fewer, thicker, and shorter afferent arterioles (6).Despite the well-recognized renal abnormalities after neonatal RAS inhibition, little is known about mechanisms by which...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Neonatal Losartan Treatment Suppresses Renal Expression of Molecules Involved in Cell-Cell and Cell-Matrix Interactions

Chen¹,

Lasaitiene²,

Gabrielsson

et al. 2004

Journal of the American Society of Nephrology

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“…The finding that Agt-deficient mice exhibit severe renal lesions shortly after birth suggests that the RAS may play a critical role in the continued development of the kidney during neonatal life. The kidney is among several tissues in which all components of the RAS cascade are expressed (33). Therefore, in addition to the local hemodynamic and volume homeostatic effects regulated by the intrarenal RAS, it remains possible that the system may also be an important regulator of kidney growth and development.…”

Section: Discussionmentioning

confidence: 99%

Complementation of reduced survival, hypotension, and renal abnormalities in angiotensinogen-deficient mice by the human renin and human angiotensinogen genes.

Davisson¹,

Kim²,

Krege³

et al. 1997

J. Clin. Invest.

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The aim of this study was to determine whether elements of the human renin-angiotensin system (RAS) could functionally replace elements of the mouse RAS by complementing the reduced survival and renal abnormalities observed in mice carrying a gene-targeted deletion of the mouse angiotensinogen gene ( mAgt ). Double transgenic mice containing the human renin ( HREN ) and human angiotensinogen ( HAGT ) genes were bred to mice heterozygous for the mAgt deletion and the compound heterozygotes were identified and intercrossed. The resulting progeny ( n ϭ 139) were genotyped at each locus and the population was stratified into two groups: the first containing both human transgenes (RA ϩ ) and the second containing zero or one, but not both human transgenes (RA Ϫ ). Despite appropriate Mendelian ratios of RA Ϫ mice that were wildtype ( ϩ / ϩ ), heterozygous ( ϩ / Ϫ ), and homozygous ( Ϫ / Ϫ ) for the deletion of mAgt at birth, there was reduced survival of RA Ϫ mAgt Ϫ / Ϫ mice to adulthood ( P Ͻ 0.001 by 2 ). In contrast, we observed appropriate Mendelian ratios of RA ϩ mAgt ϩ / ϩ , RA ϩ mAgt ϩ / Ϫ , and RA ϩ mAgt Ϫ / Ϫ mice at birth and in adults ( P Ͼ 0.05 by 2 ). These results demonstrate that the presence of both human transgenes rescues the postnatal lethality in mAgt Ϫ / Ϫ mice. The renal histopathology exhibited by RA Ϫ mAgt Ϫ / Ϫ mice, including thickened arterial walls, severe fibrosis, lymphocytic infiltration, and atrophied parenchyma, was also rescued in the RA ϩ mAgt Ϫ / Ϫ mice. Direct arterial blood pressure recordings in conscious freely moving mice revealed that BP (in mmHg) varied proportionally to mAgt gene copy number in RA ϩ mice ( ‫ف‬ 20 mmHg per mAgt gene copy, P Ͻ 0.001). BP in RA ϩ mAgt Ϫ / Ϫ mice (132 Ϯ 3, n ϭ 14) was intermediate between wild-type (RA Ϫ mAgt ϩ / ϩ , 105 Ϯ 2, n ϭ 9) and RA ϩ mAgt ϩ / ϩ (174 Ϯ 3, n ϭ 10) mice. These studies establish that the human renin and angiotensinogen genes can functionally replace the mouse angiotensinogen gene, and provides proof in principle that we can examine the regulation of elements of the human RAS and test the significance of human RAS gene variants by a combined transgenic and gene targeting approach. ( J. Clin. Invest. 1997. 99:1258-1264.)

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“…RVs undergo elaborate patterning and morphogenesis along a glomerular-collecting duct axis that is crucial for organ function. A highly developed vascular network (Gomez et al, 1997;Woolf and Loughna, 1998), interstitial support cells and a variety of distinct subregions with specialized properties that include contractile and sensory functions all contribute to the physiological actions of the kidney.…”

Section: Introductionmentioning

confidence: 99%

Identification of molecular compartments and genetic circuitry in the developing mammalian kidney

Valerius

Duah

et al. 2012

Development

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SUMMARYLengthy developmental programs generate cell diversity within an organotypic framework, enabling the later physiological actions of each organ system. Cell identity, cell diversity and cell function are determined by cell type-specific transcriptional programs; consequently, transcriptional regulatory factors are useful markers of emerging cellular complexity, and their expression patterns provide insights into the regulatory mechanisms at play. We performed a comprehensive genome-scale in situ expression screen of 921 transcriptional regulators in the developing mammalian urogenital system. Focusing on the kidney, analysis of regional-specific expression patterns identified novel markers and cell types associated with development and patterning of the urinary system. Furthermore, promoter analysis of synexpressed genes predicts transcriptional control mechanisms that regulate cell differentiation. The annotated informational resource (www.gudmap.org) will facilitate functional analysis of the mammalian kidney and provides useful information for the generation of novel genetic tools to manipulate emerging cell populations.

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Development of the kidney vasculature

Cited by 40 publications

References 31 publications

Neonatal Losartan Treatment Suppresses Renal Expression of Molecules Involved in Cell-Cell and Cell-Matrix Interactions

Neonatal Losartan Treatment Suppresses Renal Expression of Molecules Involved in Cell-Cell and Cell-Matrix Interactions

Complementation of reduced survival, hypotension, and renal abnormalities in angiotensinogen-deficient mice by the human renin and human angiotensinogen genes.

Identification of molecular compartments and genetic circuitry in the developing mammalian kidney

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