Angiotensin II Increases Pax-2 Expression in Fetal Kidney Cells Via the AT2 Receptor

Zhang, Shaoling; Moini, Babak; Ingelfinger, Julie R.

doi:10.1097/01.asn.0000130567.76794.58

Cited by 45 publications

(59 citation statements)

References 62 publications

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“…32,85 Moreover, it has been shown that angiotensin II can stimulate the expression of Pax-2 through angiotensin II type 2 receptor and, therefore, affect nephrogenesis and kidney development. 86 …”

Section: Renin-angiotensin Systemmentioning

confidence: 99%

Adult Hypertension and Kidney Disease

2006

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Abstract-Hypertension (HTN) and chronic kidney disease are highly prevalent diseases that tend to occur more frequently among disadvantaged populations, in whom prenatal care also tends to be poor. More and more evidence is emerging highlighting the important role of fetal programming in the development of adult disease, suggesting a possible common pathophysiologic denominator in the development of these disorders. Epidemiologic evidence accumulated over the past 2 decades has demonstrated an association between low birth weight and subsequent adult HTN, diabetes, and cardiovascular disease. More recently, a similar association has been found with chronic kidney disease. Animal studies and indirect evidence from human studies support the hypothesis that low birth weight, as a marker of adverse intrauterine circumstances, is associated with a congenital deficit in nephron number. The precise mechanism of the reduction in nephron number has not been established, but several hypotheses have been put forward, including changes in DNA methylation, increased apoptosis in the developing kidney, alterations in renal renin-angiotensin system activity, and increased fetal glucocorticoid exposure. A reduction in nephron number is associated with compensatory glomerular hypertrophy and an increased susceptibility to renal disease progression. HTN in low birth weight individuals also appears to be mediated in part through a reduction in nephron number. Increased awareness of the implications of low birth weight and inadequate prenatal care should lead to public health policies that may have long-term benefits in curbing the epidemics of HTN, diabetes, and kidney disease in generations to come. Key Words: hypertension Ⅲ nephron number Ⅲ kidney H ypertension (HTN) is a prevalent disorder estimated to affect Ͼ25% of the world's adult population. 1 The incidence and prevalence of chronic kidney disease (CKD) is also on the rise with Ͼ20 million people being affected in the United States alone. Two of the major causes of CKD worldwide are HTN and diabetes mellitus (DM), particularly type 2 DM. Despite many years of concerted efforts, the etiology and molecular mechanisms underlying the development of these 2 common disorders, which, in most cases, result from a complex interplay between polygenic predisposition and environmental factors, remains unclear. The frequent concurrence of HTN, type 2 DM, insulin resistance, dyslipidemia, and CKD, all of which are also important cardiovascular risk factors, may reflect a common underlying mechanism. 2 One such mechanism that is becoming more and more recognized is the far reaching impact of the fetal environment.The process through which adverse effects of an environmental insult early in life, particularly in utero, can predispose to adult disease is known as fetal programming or developmental plasticity. Fetal programming refers to the observation that an adverse environmental stimulus experienced during a critical period of development in utero can induce long-term structural and fun...

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Section: Renin-angiotensin Systemmentioning

confidence: 99%

Adult Hypertension and Kidney Disease

2006

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“…36,53 The forward and reverse primers corresponding to mouse angiotensinogen, mouse renin, and ␤-actin cDNA 36,53 in RT-qPCR assays were as follows: Mouse angiotensinogen forward primer 5Ј-CCA CGC TCT CTG GAT TTA TC-3Ј and reverse primer 5Ј-ACA GAC ACC GAG ATG CTG TT-3Ј (NM_007428), mouse renin forward primer 5Ј-CTG GCC AAG TTT GAC GGT GTT-3Ј and reverse primer 5Ј-GTG TCC ACC ACT ACC GCA CAG-3Ј (BC061053), and ␤-actin forward primer 5Ј-CGT GCG TGA CAT CAA AGA GAA-3Ј) and reverse primer 5Ј-GCT CGT TGC CAA TAG TGA TGA-3Ј (NM_007393).…”

Section: Rt-qpcrmentioning

confidence: 99%

Maternal Diabetes Modulates Renal Morphogenesis in Offspring

Tran

Chen²,

Chénier

et al. 2008

Journal of the American Society of Nephrology

117

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Maternal diabetes leads to an adverse in utero environment, but whether maternal diabetes impairs nephrogenesis is unknown. Diabetes was induced with streptozotocin in pregnant Hoxb7-green fluorescence protein mice at embryonic day 13, and the offspring were examined at several time points after birth. Compared with offspring of nondiabetic controls, offspring of diabetic mice had lower body weight, body size, kidney weight, and nephron number. The observed renal dysmorphogenesis may be the result of increased apoptosis, because immunohistochemical analysis revealed significantly more apoptotic podocytes as well as increased active caspase-3 immunostaining in the renal tubules compared with control mice. Regarding potential mediators of these differences, offspring of diabetic mice had increased expression of intrarenal angiotensinogen and renin mRNA, upregulation of NF-B isoforms p50 and p65, and activation of the NF-B pathway. In conclusion, maternal diabetes impairs nephrogenesis, possibly via enhanced intrarenal activation of the renin-angiotensin system and NF-B signaling.

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“…22,47,48 Briefly, small aliquots (20 to 50 l) of homogenized kidney explant sample were subjected to 10% SDS-PAGE and then transferred onto a polyvinylidene difluoride membrane (Hybond-P; GE Healthcare Biosciences, Baie d'Urfe, Quebec, Canada). The membrane was first blotted for anti-Pax-2 and then reblotted for ␤-actin.…”

Section: Western Blottingmentioning

confidence: 99%

“…For internal control, we deployed primers specific for mouse ␤-actin (forward and reverse primers 5Ј-CGT-GCGTGACATCAAAGAGAA-3Ј and 5Ј-GCTCGTTGCCAATAGT-GATGA-3Ј, corresponding to nucleotide sequences N ϩ 704 to N ϩ 724 and N ϩ 820 to N ϩ 840 of mouse ␤-actin cDNA [NM_007393]). 47 Immunohistochemistry Kidney explants were fixed in 4% paraformaldehyde in PBS (Fisher Scientific, Nepean, ON, Canada) after 24 h in culture and then paraffin embedded. Kidney sections of 5 m were deparaffinized in xylene and rehydrated.…”

Section: Rt-qpcrmentioning

confidence: 99%

“…22,47 In brief, firststrand cDNA was produced from 2 g of random hexamer primed total RNA using Super-Script preamplification system (Invitrogen, Burlington, Ontario, Canada). Relative quantification by real-time PCR was carried out using iQ SYBR Green Supermix Kit (Bio-Rad Laboratories, Mississauga, ON, Canada) and MiniOpticon Real-Time PCR Detection System (Bio-Rad), following the protocol described by the supplier.…”

Section: Rt-qpcrmentioning

confidence: 99%

See 1 more Smart Citation

Reactive Oxygen Species in the Presence of High Glucose Alter Ureteric Bud Morphogenesis

Zhang

Chen

Tran

et al. 2007

Journal of the American Society of Nephrology

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Renal malformations are a major cause of childhood renal failure. During the development of the kidney, ureteric bud (UB) branching morphogenesis is critical for normal nephrogenesis. These studies investigated whether renal UB branching morphogenesis is altered by a high ambient glucose environment and studied underlying mechanism(s). Kidney explants that were isolated from different periods of gestation (embryonic days 12 to 18) from Hoxb7-green fluorescence protein mice were cultured for 24 h in either normal D-glucose (5 mM) or high D-glucose (25 mM) medium with or without various inhibitors. Alterations in renal morphogenesis were assessed by fluorescence microscopy. Paired-homeobox 2 (Pax-2) gene expression was determined by real-time quantitative PCR, Western blotting, and immunohistology. The results revealed that high D-glucose (25 mM) specifically stimulates UB branching morphogenesis via Pax-2 gene expression, whereas other glucose analogs, such as D-mannitol, L-glucose, and 2-deoxy-Dglucose, had no effect. The stimulatory effect of high glucose on UB branching was blocked in the presence of catalase and inhibitors of NADPH oxidase, mitochondrial electron transport chain complex I, and Akt signaling. Moreover, in in vivo studies, it seems that high glucose induces, via Pax-2 (mainly localized in UB), acceleration of UB branching but not nephron formation. Taken together, these data demonstrate that high glucose alters UB branching morphogenesis. This occurs, at least in part, via reactive oxygen species generation, activation of Akt signaling, and upregulation of Pax-2 gene expression.

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Angiotensin II Increases Pax-2 Expression in Fetal Kidney Cells Via the AT2 Receptor

Cited by 45 publications

References 62 publications

Adult Hypertension and Kidney Disease

Adult Hypertension and Kidney Disease

Maternal Diabetes Modulates Renal Morphogenesis in Offspring

Reactive Oxygen Species in the Presence of High Glucose Alter Ureteric Bud Morphogenesis

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