Discipline: Biological Sciences
Subcategory: Physiology and Health
Petra Guzman - California State University, Los Angeles
Co-Author(s): Dr. Katrina Yamazaki
Type 2 diabetes (T2D) causes microvascular diseases in the kidney leading to decrease oxygen delivery and cell death. This triggers fibrosis and loss of kidney function. T2D and fibrosis has been linked by hypoxia-inducible factor (HIF)-1, a protective transcription factor that should be expressed during low oxygen tensions. However, studies have demonstrated repressed HIF-1 activity in T2D with the mechanisms unknown. The major objective of my study is to investigate the link between T2D, HIF-1 and the Angiotensin II (Ang II) signaling pathway, which is known to induce HIF-1 expression in response to low blood flow to the kidneys. I hypothesize that the Ang II signaling pathway is being hindered in the setting of T2D, leading to repressed HIF-1 and fibrosis. Using an in vivo model of T2D, blood and kidney tissue from diabetic mice were used for biochemical assays (i.e. Western blot, PCR, histology, etc.) to analyze protein expression, gene expression and stain for collagen/new blood vessels. iNOS expression, a major producer of nitric oxide, was evaluated by western blot and demonstrated an increase expression in the T2D group versus control. Abnormally high levels of nitric oxide, a free radical, can lead to oxidative damage in the cell. More work is needed to determine if increased production of free radicals in T2D leads to oxidative damage of the AngII receptor or its downstream components to prevent the expression of HIF-1. Results from this study may lead to the development of new treatments that target renal fibrosis in T2D.Not Submitted
Funder Acknowledgement(s): Louis Stokes Alliances for Minority Participation (LSAMP); LSAMP Undergraduate Grant (HRD-1302873); NSF.
Faculty Advisor: Katrina Yamazaki, Katrina.Yamazaki@calstatela.edu
Role: Majority of the work was done by myself, with the guidance of my faculty mentor.