Kidney development in the nitrofen-induced pulmonary hypolasia and congenital diaphragmatic hernia in rats

Montedónico, Sandra; Nakazawa, Nana; Shinkai, Toko; Bannigan, John; Puri, Prem

doi:10.1016/j.jpedsurg.2006.09.062

Cited by 6 publications

(5 citation statements)

References 16 publications

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“…Regarding potential fetal adverse effects, the nitrofen-exposed pups presented decrease of HW/BW and KW/BW ratios as previously documented (10,(61)(62)(63). On the other hand, PD-123319 beneficial effect seemed lungspecific, since HW/BW and KW/BW ratios of the pups were not altered.…”

Section: Discussionsupporting

confidence: 76%

Local Fetal Lung Renin-Angiotensin System as a Target to Treat Congenital Diaphragmatic Hernia

Nogueira‐Silva

Carvalho-Dias

Piairo

et al. 2011

Mol Med

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Antenatal stimulation of lung growth is a reasonable approach to treat congenital diaphragmatic hernia (CDH), a disease characterized by pulmonary hypoplasia and hypertension. Several evidences from the literature demonstrated a possible involvement of renin-angiotensin system (RAS) during fetal lung development. Thus, the expression pattern of renin, angiotensin-converting enzyme, angiotensinogen, type 1 (AT 1 ) and type 2 (AT 2 ) receptors of angiotensin II (ANGII) was assessed by immunohistochemistry throughout gestation, whereas the function of RAS in the fetal lung was evaluated using fetal rat lung explants. These were morphometrically analyzed and intracellular pathway alterations assessed by Western blot. In nitrofen-induced CDH model, pregnant rats were treated with saline or PD-123319. In pups, lung growth, protein/DNA ratio, radial saccular count, epithelial differentiation and lung maturation, vascular morphometry, right ventricular hypertrophy and overload molecular markers, gasometry and survival time were evaluated. Results demonstrated that all RAS components were constitutively expressed in the lung during gestation and that ANGII had a stimulatory effect on lung branching, mediated by AT 1 receptor, through p44/42 and Akt phosphorylation. This stimulatory effect on lung growth was mimicked by AT 2 -antagonist (PD-123319) treatment. In vivo antenatal PD-123319 treatment increased lung growth, ameliorated indirect parameters of pulmonary hypertension, improved lung function and survival time in nonventilated CDH pups, without maternal or fetal deleterious effects. Therefore, this study demonstrated a local and physiologically active RAS during lung morphogenesis. Moreover, selective inhibition of AT 2 receptor is presented as a putative antenatal therapy for CDH.

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Section: Discussionsupporting

confidence: 76%

Local Fetal Lung Renin-Angiotensin System as a Target to Treat Congenital Diaphragmatic Hernia

Nogueira‐Silva

Carvalho-Dias

Piairo

et al. 2011

Mol Med

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“…However, this hypothesis has been challenged by other investigators who did not find the kidney to be enlarged either in human autopsy or in teratogenic model of CDH [4,15]. Moreover, we have recently demonstrated that kidneys are hypoplastic in nitrofen-exposed foetuses compared to controls [5]. In this study, not only the kidney weight but also kidney/ body ratio were significantly decreased in CDH model compared to controls.…”

Section: Discussioncontrasting

confidence: 56%

“…The association of pulmonary hypoplasia and disturbance of foetal renal function suggests that there may be a relationship between lung and kidney development [2,3]. It has recently been demonstrated that kidneys are hypoplastic in the nitrofen model of CDH [4,5]. However, the precise pathogenesis of renal hypoplasia in CDH is still not clearly understood.…”

Section: Introductionmentioning

confidence: 99%

Altered renin–angiotensin system gene expression causes renal hypoplasia in the rats with nitrofen-induced diaphragmatic hernia

et al. 2005

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The association between renal hypoplasia and pulmonary hypoplasia in congenital diaphragmatic hernia (CDH) has become recently appreciated. However, the underlying mechanisms responsible for this association are still unknown. Renin-angiotensin system (RAS) plays an important role in renal and somatic growth, angiogenesis and reproduction. We hypothesized that abnormal expression of RAS components may be responsible for renal hypoplasia in CDH. We therefore designed this study to examine the gene expression of main components of RAS in the kidney of nitrofen-induced CDH in the rat. Pregnant rats were exposed to either olive oil or 100 mg of nitrofen on day 9.5 of gestation. Foetuses were recovered at term and divided into three groups: control (n=8), nitrofen without CDH (n=8) and CDH (n=8). Reverse transcription polymerase chain reaction was performed to evaluate the relative amount of angiotensinogen (AGT), angiotensin II type 1 receptor with 1a and 1b subtypes (AT(1a)R and AT(1b)R), angiotensin II type 2 receptor (AT(2)R), angiotensin-converting enzyme (ACE) and renin expression in the kidney. AT(1a)R, AT(1b)R, AT(2)R, AGT and renin levels were significantly decreased in the kidney of CDH rats compared with controls. We did not find a significant difference in ACE between CDH animals and controls. Our data show that the downregulation of RAS may play an important role in the pathogenesis of renal hypoplasia in the nitrofen-induced CDH.

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“…However, the relationship of the developing lung and kidney is not completely understood. Renal enlargement has been reported in association with pulmonary hypoplasia in congenital diaphragmatic hernia [16]. …”

Section: Discussionmentioning

confidence: 99%

Hereditary renal adysplasia, pulmonary hypoplasia and Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: a case report

Acién

Galán

Manchón

et al. 2010

Orphanet J Rare Dis

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BackgroundHereditary renal adysplasia is an autosomal dominant trait with incomplete penetrance and variable expression that is usually associated with malformative combinations (including Müllerian anomalies) affecting different mesodermal organs such as the heart, lung, and urogenital system.Case reportA case showing pulmonary hypoplasia, hip dysplasia, hereditary renal adysplasia, and Mayer-Rokitansky-Kuster-Hauser syndrome in adulthood is reported here. The i.v. pyelography showed right renal agenesis with a normal left kidney and ureter. Ultrasound and Magnetic Resonance Imaging also showed right renal agenesis with multicystic embryonary remnants in the right hemipelvis probably corresponding to a dysgenetic kidney. An uretrocystoscopy showed absence of ectopic ureter and of the right hemitrigone. She was scheduled for a diagnostic laparoscopy and creation of a neovagina according to the McIndoe technique with a prosthesis and skin graft. Laparoscopy confirmed the absence of the uterus. On both sides, an elongated, solid, rudimentary uterine horn could be observed. Both ovaries were also elongated, located high in both abdominal flanks and somewhat dysgenetics. A conventional cytogenetic study revealed a normal female karyotype 46, XX at a level of 550 GTG bands. A CGH analysis was performed using a 244K oligoarray CGH detecting 11 copy number variants described as normal variants in the databases. The 17q12 and 22q11.21 microdeletions described in other MRKH patients were not present in this case. Four years after operation her evolution is normal, without symptoms and the neovagina is adequately functional. The geneticists have studied her family history and the pedigree of the family is shown.ConclusionsWe suggest that primary damage to the mesoderm (paraaxil, intermediate, and lateral) caused by mutations in a yet unidentified gene is responsible for: 1) skeletal dysplasia, 2) inappropriate interactions between the bronchial mesoderm and endodermal lung bud as well as between the blastema metanephric and ureteric bud, and eventually 3) Müllerian anomalies (peritoneal mesothelium) at the same level. These anomalies would be transmitted as an autosomal dominant trait with incomplete penetrance and variable expressivity.

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Kidney development in the nitrofen-induced pulmonary hypolasia and congenital diaphragmatic hernia in rats

Cited by 6 publications

References 16 publications

Local Fetal Lung Renin-Angiotensin System as a Target to Treat Congenital Diaphragmatic Hernia

Local Fetal Lung Renin-Angiotensin System as a Target to Treat Congenital Diaphragmatic Hernia

Altered renin–angiotensin system gene expression causes renal hypoplasia in the rats with nitrofen-induced diaphragmatic hernia

Hereditary renal adysplasia, pulmonary hypoplasia and Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: a case report

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