Discipline: Biological Sciences
Subcategory: Physiology and Health
Petra Guzman - California State University, Los Angeles
Co-Author(s): Katrina Yamazaki, California State University, Los Angeles
Type 2 diabetes is a metabolic disease that is known to cause organ damage arising from microvascular diseases. One such complication includes kidney damage resulting from renal fibrosis. Renal fibrosis leads to in the scarring of the kidney tissue and subsequent loss of function that is vital to maintaining homeostasis within the body. One important function that is lost is the ability of the nephrons to filter blood thus leading to water and salt imbalance, thereby affecting blood volume and blood pressures. One possible factor that can link type 2 diabetes and renal fibrosis include a transcription factor that mediates the adaption of cells to low oxygen tensions, known as Hypoxia-Inducible Factor (HIF)-1. Normally, one would expect HIF-1 to be activated in type 2 diabetes due to loss of oxygen delivery due to microvascular damage; however, studies have demonstrated repressed HIF-1 activity in the diabetic kidney. The precise mechanism is unknown and will be the objective of my project. It is known that Angiotensin II (Ang II), a peptide hormone released in response to low blood flow to the kidneys, induces HIF-1α. It may be possible that Ang II production or its signaling pathway after activation of its receptor is being hindered in the setting of type 2 diabetes. Therefore our objective is to investigate how the impairment of Ang II decreases the HIF-1α activity. We will investigate this by using in vivo studies using a control group and a diabetic group of mice. At 28 weeks, blood and kidney tissue samples will be collected from each group. Western blot analysis will be used to look at protein expression of the AngII receptor, AT1, HIF-1α and proteins involved in the Ang II-AT1 receptor signaling pathway. PCR will be used to evaluate expression of genes controlled by HIF-1α. Histology, such as Masson trichome stain for collagen and immunostaining to view new blood vessels, will also be conducted. In order to analyze Ang II levels in the blood an Ang II ELISA Kit will be used. Our anticipated results include high levels of Ang II in the blood with decreased expression of its receptor as well as decrease expression of genes regulated by HIF-1. We also expect to see evidence of renal fibrosis with a decrease in new blood vessels as determined by histological analysis of the kidney tissues. This project will give a better understanding on the development of renal fibrosis and type 2 diabetes. It will also develop a deeper study involving factors in the human body, such as hormones, proteins, pathways, and how they are affected in a diabetic setting.
References: Xiao, H., Gu, Z., Wang, G., and Zhao, T. (2013) The Possible Mechanisms Underlying the Impairment of HIF-1α Pathway Signaling in Hyperglycemia and the Beneficial Effects of Certain Therapies. International Journal of Medical Sciences Int. J. Med. Sci. 10, 1412-1421. Chu, K., and Leung, P. (2009) Angiotensin II in Type 2 Diabetes Mellitus. Current Protein & Peptide Science CPPS 10, 75-84.
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: With the guidance of my faculty mentor I was able to develop the question and majority of the work will be done by myself and with my mentor.