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Study of the effects of an ofidian metalloproteinase in preadipocytes: activation of inflammatory response and cell differentiation

Grant number: 17/19733-9
Support type:Scholarships in Brazil - Master
Effective date (Start): March 01, 2018
Effective date (End): December 31, 2019
Field of knowledge:Biological Sciences - Pharmacology - Toxicology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Catarina de Fatima Pereira Teixeira
Grantee:Priscila Signor Motta
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated research grant:15/50040-4 - Rational approach for searching molecular targets involved in inflammatory events and cell survival, AP.PCPE

Abstract

Snake venoms of the Viperidae family contain proteinases of the metalloproteinases class, with potent inflammatory activity. These enzymes exhibit structural and functional homology with mammalian metalloproteinases (MMPs) whose levels are elevated in serum and joint fluid of patients with inflammatory arthropathies. Thus, venom metalloproteinases are useful tools for elucidating the actions of this class of enzymes. Inflammatory arthropathies, such as osteoarthritis and rheumatoid arthritis, with a high incidence worldwide, are among the main causes of movement limitation and incapacitation and represent a risk factor for the loss of health in the contemporary society. MMPs, in addition to the degradation of articular cartilage, have been shown to exert inflammatory effects in the joint and to activate inflammatory cells. The articular adipose tissue, in close contact with the synovial membrane and cartilage of the knee, has the capacity to secrete a range of inflammatory mediators and growth factors in the joint cavity, playing an important role in triggering and progression of joint inflammation. However, the action of metalloproteinases on major cells of the adipose tissue are unknown. In this study, the effects of BmooMPI-alpha metalloproteinase, isolated from Bothrops moojeni venom, on preadipocytes in culture will be investigated focusing on (1) synthesis of inflammatory mediators (cytokines, chemokines, adipocytokines and PGE2), (2) mechanism of PGE2 release, a crucial factor in the differentiation of preadipocytes, and (3) the differentiation of these cells into mature adipocytes. This study will allow a better understanding of the mechanisms by which metalloproteinases trigger inflammatory events, target cells and their effects on the joints. Therefore, the design of new pharmacological compounds for confrontation of joint inflammation may be obtained. (AU)