Intrauterine low-protein diet aggravates developmental abnormalities of the urinary system via the Akt/Creb3 pathway in Robo2 mutant mice.

This study aimed to establish an intrauterine low protein diet Robo2 mutant mouse model and found that intrauterine low-protein diet led to significantly increased CAKUT phenotypes in Robo2PB/+ mice offspring, dominant by a duplicated collecting system. At the same time, more ectopic and lower-located ureteric buds (UB) were observed under intrauterine low-protein diet Robo2 mutant mouse model and the number of UB branches was reduced in the serum-free culture. During UB protrusion, intrauterine low-protein diet reduced the expression of Slit2/Robo2 in the Robo2 mutant mice and affected the expression of Gdnf/Ret, which is a key molecule for metanephric development, with increasing p-Akt and p-Creb3 activity and reducing apoptotic cells in E11.5 UBs tissues. The mechanism by which intrauterine low-protein diet aggravates CAKUT in Robo2 mutant mice may be related to the disruption of Akt/Creb3 signaling and a reduction in the apoptosis in UBs tissue. PMID: 31630547 [PubMed - as supplied by publisher]
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research