STUDY OF ANNEXIN A1 PROTEIN IN STREPTOZOTOCIN-INDUCED DIABETIC NEPHROPATHY IN MICE

Abstract

In Brazil, there are currently more than 15.5 million people (20-79 years old) living with diabetes mellitus (DM), ranking sixth among the top 10 countries with the disease. In the kidneys, high circulating glucose levels lead to excessive production of reactive oxygen species (ROS) by mitochondria, generating activation of oxidativestress. Furthermore, the production of ROS is associated with the processes of lipidperoxidation, depletion of sulfhydryl groups, alteration of different signal transductionpathways, among other actions, which can cause damage to DNA and, consequently, cell apoptosis. In this context, annexin A1 (AnxA1), a 37 kDa anti-inflammatory protein, stands out, which in addition to mediating several steps of the inflammatoryresponse, is involved in important pathophysiological roles including cell proliferation,differentiation and apoptosis. However, its role in regulating renal oxidative stress has been little explored. Therefore, the general objective of the work will be to evaluatethe role of AnxA1 in streptozotocin (STZ) - induced diabetic nephropathy in mice. DM will be induced by intraperitoneal injection (5 consecutive days) of STZ (65 mg/kg) in male C57BL/6 wild-type (WT) and AnxA1 knockout (AnxA1-/-) mice. In control ofanimals, the vehicle will be administered. On days 30, 60 and 90 the animals will beweighed and circulating glucose will be measured. On day 90, the animals will be euthanized to collect blood and kidneys. The following analyzes will be carried out: histological, immunohistochemistry and western blotting to detect the expression of AnxA1/Fpr2 receptor and oxidative stress markers, measurement of the activity ofoxidizing and antioxidant enzymes by colorimetric assays. Thus, the development of this study will contribute to the understanding of the role of AnxA1 in renal biology in terms of cellular and molecular mechanisms during DM.