ROLE OF ANNEXIN A1 IN SPLEEN BIOLOGY: STUDY IN EXPERIMENTAL MODELS OF DIABETES (DM)

• Grant number: 24/20362-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Adriana Degrossoli
• Grantee: Laura Santana de Chiara
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Diabetes mellitus (DM) is a serious public health problem worldwide, affecting 15.5 million people in Brazil. DM is characterized by systemic dysregulations that affect various tissues, including the spleen. The changes observed in the spleen include an increase in size, fibrosis, and a reduction in the number of lymphocytes and progenitor cells, which can affect its immune function. Oxidative stress, induced by hyperglycemia and important in the etiology of DM, is a possible mechanism for splenic changes in this context. Patients with type 2 DM (DM2) have high plasma levels of annexin A1 (AnxA1), an oxidative stress-induced protein that mediates various stages of the inflammatory response and is involved in functions such as cell proliferation, differentiation, and apoptosis. In a mouse model of DM2, AnxA1 helped ameliorate the effects of insulin resistance. However, its role in the spleen in type 1 DM (DM1) has been little studied. The aim of this project is to evaluate the role of AnxA1 in spleen biology in a mouse model of DM1. DM1 will be induced by intraperitoneal injection of streptozotocin (STZ) in wild type (WT) and AnxA1 knockout (AnxA1-/-) male C57Bl/6 mice. After 90 days of DM1 induction, the animals' spleens will be harvested for analysis of morphological changes by histological techniques, differentiation of immune cell types by immunohistochemistry, detection of AnxA1 expression and oxidative stress markers by Western blotting, and measurement of oxidant and antioxidant enzyme activity by colorimetric assays. These results may broaden our understanding of the role of AnxA1 in the pathogenesis of DM, particularly in the morphological and functional alterations of the spleen.