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Dr. Yan Zhang
Research Professor
Michigan Technological University

Targeting liver kinase B1 in human polycystic kidney disease 

Abstract: Autosomal dominant polycystic kidney disease (ADPKD) is the most common, potentially lethal genetic disorder characterized by the progressive enlargement of numerous fluid-filled cysts and the development of interstitial inflammation and fibrosis. Approximately 50% of patients progress to end-stage renal disease by middle age and require dialysis or renal transplantation. Currently, treatment options for ADPKD patients are limited; thus, the development of new effective therapies is urgent. Liver kinase B1(LKB1) is an important regular of cell metabolism, proliferation, and polarity but its role in human ADPKD remain unclear. Our experiment results showed that LKB1 signaling pathway was dysregulated in human ADPKD kidneys. Renal tubule-specific knockout of LKB1 accelerated cyst growth and renal fibrosis of PKD mice whereas activation of LKB1 decreased cyst growth and preserved kidney function. Thus, our data demonstrate that LKB1 is a potential therapeutic target for ADPKD treatment.