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Maternal protein restriction reduces perlecan at mid-metanephrogenesis in rats
Xiao-Shan Tang1, Qian Shen1, Jing Chen1
1Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai, China.
Insights
Maternal protein restriction in pregnant rats reduced offspring nephron number by altering perlecan expression and affecting cell proliferation and apoptosis during kidney development.
Area of Science:
- Developmental Biology
- Renal Physiology
- Nutritional Science
Background:
- Maternal protein restriction during pregnancy is linked to reduced offspring nephron number and increased risk of chronic kidney disease.
- Perlecan, a key heparan sulfate proteoglycan (HSPG), is vital for kidney development and nephron formation.
Purpose of the Study:
- To investigate the impact of maternal dietary protein restriction on perlecan expression during fetal kidney development.
- To correlate altered perlecan expression with changes in cell proliferation and apoptosis in offspring kidneys.
Main Methods:
- Pregnant rats were fed either a low-protein (MLP) or normal-protein (MNP) diet.
- Embryonic kidneys were analyzed for rHSPG2 (perlecan gene) transcript levels via RT-PCR and protein expression via immunohistochemistry.
- Cell proliferation (Ki67) and apoptosis (TUNEL) were assessed at different developmental stages.
Main Results:
- Maternal protein restriction significantly reduced embryonic weights and nephron numbers.
- Reduced rHSPG2 transcript and protein levels were observed in the MLP group during embryonic and neonatal periods.
- The MLP group exhibited decreased cell proliferation and increased apoptosis in developing kidneys.
Conclusions:
- Maternal protein restriction disrupts normal kidney development by downregulating perlecan expression.
- Aberrant cell proliferation and apoptosis contribute to the reduced nephron number observed in offspring of protein-restricted mothers.
- Findings offer insights into mechanisms underlying developmental programming of kidney disease.
Aim:
Maternal dietary protein restriction reduces nephron number in offspring and increases the risk of cardiovascular and chronic kidney diseases. Perlecan is the major basement membrane/extracellular matrix heparan sulfate proteoglycan (HSPG) that plays a crucial role in nephron formation. This study was to determine whether maternal dietary protein restriction during pregnancy leads to an abnormal perlecan expression pattern during kidney development and a correlation with aberrant cell proliferation and apoptosis.
Methods:
Pregnant Sprague-Dawley rats were divided into two groups, maintained on either a low-protein diet (MLP group) or a normal-protein diet (MNP group). Kidneys were dissected from embryos of different kidney development stages. Real-time PCR and immunohistochemistry were performed to detect the transcript level of rHSPG2, the coding gene of perlecan, and its protein expression pattern. Apoptosis and proliferation cell were detected by TUNEL system and Ki67 marker.
Results:
Embryonic weights and nephron number were significantly affected by maternal low protein diets. The transcript level of rHSPG2 in the MLP group was significantly lower at embryonic day 18 and the neonatal period. Immunohistochemistry study was consistent with the RT-PCR results. The proliferation level of the MLP group was significantly lower than the MNP group at E18 and more apoptotic cells was detected in MLP newborn.
Conclusion:
Maternal protein restriction reduced the expression of perlecan and lead aberrant cell proliferation and apoptosis during mid-metanephrogenesis in offspring. This data may provide new evidence to understand the mechanism of reduced nephron number due to maternal protein restriction and enlighten solution.
