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 and chronic kidney disease (CKD) in adulthood. The exact reasons for this phenomenon, called perinatal programming, are not well-defined. Moreover, this perinatal programming occurring in progeny of diabetic mothers could be further influenced after a 'second hit' during postnatal life-e.g., chronic exposure to factors including smoking, physiological stress, high-salt consumption or high fat diet, excessive alcohol consumption and a sedentary lifestyle, etc.. Therefore, knowledge of how HTN and CKD develop in at-risk people born to mothers with diabetes will lead to improved prevention/treatment strategies. 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 is associated with impaired kidney development in young offspring of diabetic dams. This proposal aims to understand the molecular bases of Hhip impact on maternal diabetes-induced renal programming of HTN and CKD in adult offspring. We will perform the studies using Hhip knock-out mouse model and kidney cells grown in petri dishes to define the physiological role of Hhip in maternal diabetes-induced renal programming. We expect the present project to generate a comprehensive understanding of Hhip impact on maternal diabetes-induced renal programming of CKD; facilitate the identification of novel drug targets to prevent/reduce the long-term risks of complications in the progeny of diabetic mothers; and reduce diabetic pregnancy-associated healthcare burdens in Canada and thereby improve the quality of life of Canadians.