Grant: Project Grant

Pregnancy with diabetes or gestational diabetes (i.e., maternal diabetes) creates elevated blood sugar levels in the womb, resulting in a variety of birth defects. In addition, there are lifelong consequences for the offspring-increased tendency to develop various disorders, such as metabolic syndrome, hypertension (HTN), obesity, cardiovascular disease (CVD) and chronic kidney disease (CKD) in adulthood. The exact reasons for this phenomenon, called perinatal programming, are not well-defined. We recently discovered that high blood sugar levels in the pregnant mother turn on the expression of a molecule called the hedgehog interacting protein (Hhip), which modulates kidney development in the womb and optimizes cell functions in adults. Our specific objective is to investigate the physiological role of the Hhip in maternal diabetes-induced perinatal programming and to explore whether Hhip could be used as a biomarker to monitor or predict the development of HTN and CKD in the offspring. We will perform the studies using Hhip deficient and Hhip overexpression mouse models and kidney cells grown in petri dishes to define the physiological role of Hhip in fetal kidney developments and in perinatal programming. Moreover, we will measure Hhip levels in mouse blood and urine samples to determine whether Hhip could be used as a biomarker to monitor or predict the development of HTN and CKD in the offspring to facilitate translation our results from the bench to bedside. The goal is to gain new insights and help researchers and clinicians to develop HTN and CKD prevention and treatment approaches, with a view to reducing diabetic pregnancy-associated healthcare burdens in Canada and thereby improve the quality of life of Canadians.