THE ROLE OF HEPATOCYTE GROWTH FACTOR IN LONG-TERM RENAL RECOVERY AFTER ACUTE KIDNEY INJURY IN MICE

Open Access
Author:
Pease, Lauren E
Area of Honors:
Biochemistry and Molecular Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Lorraine C Santy, Thesis Supervisor
  • Wendy Hanna-Rose, Honors Advisor
Keywords:
  • renal iri
  • acute kidney injury
  • ischemia and reperfusion injury
  • HGF
  • cytohesin-2/ARNO
  • mice
Abstract:
While advancements have been made in identification of acute kidney injury (AKI), much is still unknown as to how to treat the disease. AKI affects approximately 13.3 million people per year, and its mortality rate has not decreased significantly in the past 20 years. Additionally, AKI is associated with high morbidity, elevated hospital costs, and approximately 1.7 million deaths per year, and it can lead to chronic kidney disease and end-stage renal disease in survivors. Thus, it is extremely important to study possible treatments for this potent disease. The aim of this project was to identify whether treatment with hepatocyte growth factor (HGF) in mice with AKI would improve kidney recovery. HGF is the signaling molecule for a c-Met receptor that, through a signaling cascade, leads to the activation of Rac1. Rac1 activation results in epithelial cell migration, which is necessary to repopulate the basement membrane after injury. Because it is known that HGF levels are increased after IRI, it was hypothesized that HGF injections would significantly decrease fibrosis. Additionally, since cytohesins are known to be GEFs in the Rac1 activation pathway, it was hypothesized that treatment with cytohesin inhibitor, SecinH3, would inhibit the recovery pathway and result in more fibrosis. While the HGF treated mice did not display significantly less fibrosis than the vehicle treated mice, those that received the HGF treatment did have a lower average percent fibrosis and did differ significantly from the mice treated with SecinH3 and SecinH3/HGF. Additionally, the mice that received the SecinH3 and SecinH3/HGF treatment differed significantly from those that received the vehicle treatment. These results show that activation of Rac1 is important to kidney recovery, and the percent fibrosis averages suggest that future studies may find HGF treatment to significantly decrease fibrosis when compared to the vehicle.