Evaluation of annexin A1 protein immunomodulatory activity in cutaneous and placental lesions resulting from Diabetes Mellitus

Abstract

Annexin A1 (ANXA1) is a 37 kDa protein that exhibits calcium and membrane phospholipid binding sites and is involved in the inhibition of glucocorticoid-induced eicosanoid and phospholipase A2 synthesis, which gives antiinflammatory properties to this protein. Several studies have shown the protective effect of ANXA1 on acute and chronic inflammatory processes in response to infection and autoimmune diseases. In addition to inflammatory events, the actions of ANXA1 have been poorly studied in tissue regeneration processes, especially in the regeneration and repair of damaged tissues and in wound healing. Further analysis of the various biological activities described for ANXA1, especially in the control of proliferation and apoptosis, and investigating the role of this protein in trophoblast biology and the modulation of markers related to the survival of these cells, is extremely important for understanding normal placental development and diseases such as Gestational Diabetes Mellitus (GDM). For these reasons, the proposed projects are related to the investigation of this protein through analyzes on experimental skin lesions and human placental pathophysiology to evaluate its therapeutic potential in the possible complications related to Diabetes Mellitus (DM). In the first proposal, in the in vivo model of a skin lesion, after standardizing the viable technique of an anionic gel with peptide AnxA12-26, it will be evaluated in relation to the healing properties of these lesions in type 1 DM (T1DM). The second proposal will identify the role of ANXA1 in placental cell survival and infer a potential mechanism (related to DNA damage and repair) that could relate ANXA1 to placental cell survival in GDM. In the proposed projects, different methodologies will be employed such as: AnxA12-26 anionic gel formulation, immunohistochemical reactions for inflammatory and molecular mediators (such as oxidative DNA damage and double DNA breakdown), Western blot, etc., involving strategies that will enable the detailed understanding of ANXA1 activity in the proposed aspects and its possible therapeutic applications. (AU)