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Altered renin-angiotensin system gene expression causes renal hypoplasia in the rats with nitrofen-induced
Boris Chertin1, Nana Nakazawa, Sandra Montedonico
1Children's Research Centre, Our Lady's Hospital for Sick Children, Crumlin, Dublin 12, Ireland.
Abstract:
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.
Insights
Congenital diaphragmatic hernia (CDH) is linked to kidney issues. This study found that reduced renin-angiotensin system (RAS) gene expression in CDH rat kidneys may cause renal hypoplasia, a key finding for understanding CDH complications.
Area of Science:
- Developmental biology
- Genetics
- Nephrology
Background:
- Congenital diaphragmatic hernia (CDH) is associated with renal hypoplasia, but the mechanisms are unclear.
- The renin-angiotensin system (RAS) is crucial for growth and organ development.
Purpose of the Study:
- To investigate the role of RAS gene expression in renal hypoplasia in a rat model of CDH.
- To test the hypothesis that abnormal RAS component expression contributes to kidney underdevelopment in CDH.
Main Methods:
- A nitrofen-induced CDH rat model was used.
- Kidney gene expression of RAS components (AGT, AT1aR, AT1bR, AT2R, ACE, renin) was analyzed using RT-PCR in control and CDH fetuses.
Main Results:
- Significant downregulation of angiotensinogen (AGT), AT1aR, AT1bR, AT2R, and renin was observed in the kidneys of CDH rats compared to controls.
- No significant difference in angiotensin-converting enzyme (ACE) expression was found between groups.
Conclusions:
- Downregulation of the renin-angiotensin system (RAS) likely plays a significant role in the pathogenesis of renal hypoplasia associated with congenital diaphragmatic hernia (CDH).
- These findings highlight a potential molecular pathway contributing to CDH-related kidney abnormalities.
