Dynamic p53 protein expression and phosphorylation in the kidneys of rats that experienced intrauterine growth restriction.

AIM: This study investigated the mechanisms involved in intrauterine growth restriction (IUGR).

METHODS

The IUGR model was established by feeding pregnant SD rats a low-protein diet. Protein expression and phosphorylation were detected using Western blot and/or immunohistochemistry. Cell apoptosis was detected by TUNEL staining. The MDM2 mRNA expression was measured by real-time PCR.

RESULTS

Pups from the IUGR group had significantly lower body (7th day, 2 months) and kidney weights (1st day, 7th day, 2 months) compared to pups from the control group (p < 0.01). The glomeruli number in IUGR pups was significantly less than that in the control pups at 2 and 3 months after birth (p < 0.01). p53 protein level and p53 phosphorylation at Ser(15) were time-dependently decreased in the kidney at 1st day, 7th day, 21st day, 2 months and 3 months, but their levels in the kidney of the IUGR pups was significantly higher than that in control pups at each time point (p < 0.05, p < 0.01, or p < 0.001). Significantly more positive p21 staining was observed in IUGR pups than in control pups at each time point. Real-time PCR of MDM2 mRNA expression showed no significant difference between IUGR and control pups (p > 0.05). Significant apoptosis was observed in the kidneys of IUGR pups compared to control pups.

CONCLUSION

Malnutrition-induced IUGR may be associated with the activation of p53-p21 signaling in the kidney.