STUDY OF ANNEXIN A1 EXPRESSION IN THE LUNG UNDER ESTROGEN DEPLETION IN EXPERIMENTAL TYPE 1 DIABETES MELLITUS

• Grant number: 26/11432-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2026
• End date: July 31, 2027
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Cristiane Damas Gil
• Grantee: Gabriella Ferreira de Oliveira
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Type 1 Diabetes Mellitus (T1DM), an autoimmune disease characterized by the destruction of pancreatic beta cells, results in insulin deficiency and triggers systemic metabolic and inflammatory changes. Recent evidence indicates that the lung is an important target organ for these alterations, presenting thickening of the alveolar-capillary membrane, impaired gas diffusion, and structural changes associated with chronic hyperglycemia and the formation of advanced glycation end products. In this context, estrogen depletion, as observed in menopause, can exacerbate these alterations by compromising regulatory mechanisms of inflammation and tissue homeostasis, favoring an increase in inflammatory infiltrate and remodeling of the extracellular matrix. Annexin A1 (AnxA1), a protein with anti-inflammatory and pro-resolution properties, has been implicated in modulating the immune response and limiting tissue damage. However, its role in the pulmonary pathophysiology of T1DM, especially in association with estrogen depletion, remains poorly understood. Thus, this study aims to evaluate the effects of estrogen depletion associated with experimental type 1 diabetes mellitus (T1DM) on pulmonary structural and inflammatory alterations, with emphasis on AnxA1 expression, in female mice. The animals will be divided into four experimental groups: SHAM, OVX, DM, and OVX+DM. Ovariectomy will be performed prior to the induction of T1DM by streptozotocin. The animals will be monitored for body weight and blood glucose levels, and the lungs will be collected at the end of the experiment. Analyses will include histological and histomorphometric evaluation of the pulmonary parenchyma, with measurement of alveolar septum thickening and collagen deposition, as well as quantification of inflammatory infiltrate by immunohistochemistry and AnxA1 and its receptor expression by immunohistochemistry and western blotting. It is expected that the results will contribute to the understanding of the mechanisms that associate T1DM and estrogen depletion with pulmonary alterations, highlighting the possible involvement of AnxA1 in the modulation of these processes. (AU)