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Role of the protein SPAG11 in the modulation of experimental arthritis

Grant number: 09/12375-3
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): December 01, 2009
Effective date (End): November 30, 2013
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal Investigator:Maria Christina Werneck de Avellar
Grantee:Alexandre Denadai Souza
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated scholarship(s):12/07784-4 - Analysis of the effect of heterologous expression of hSPAG11B alternative splice variants in the development of inflammatory arthritis in the knee joint of wild-type and F2rl1 (PAR2) knockout mice, BE.EP.PD


Joint diseases like Osteoarthritis (OA) and Rheumatoid Arthritis (RA) regard to a class of inflammatory diseases highly degenerative, in which the last stage is associated with the irreversible loss of articular cartilage. The Proteinase-Activated Receptor 2 (PAR2) has been hypothesised as a pivotal mediator of joint inflammation, considering that its activation induces joint swelling, leukocyte recruitment, activation of transcription factors like nuclear factor - KB (NFKB) and production of cytokines like IL-1beta and TNF-alpha. This receptor is activated by the proteolysis of its N-terminus by extracellular serine-proteinases like mast cell tryptase. This proteinase, besides its involvement in the process cited above, is also involved in the extracellular matrix turnover, directly via its collagenase activity and indirectly by activating latent metalloproteinases and aggrecanases. On the other hand, it was reported recently that the isoform D of the human SPAG11 gene (sperm associated antigen 11) interacts physically and inhibits competitively the mast cell tryptase. Although SPAG11 isoforms were first cloned from male reproductive tract, preliminary evidences from Dr. Avellar´s group have showed that SPAG11 isoforms are also expressed in hypertrophic condrocytes during the embryonic development of Wistar rat. Interestingly, these are the same cells where PAR2 is highly expressed. Thus, we have hypothesised that products of the SPAG11 gene may be involved in the modulation of extracellular matrix turnover via inhibition of tryptase/PAR2 activity. Therefore, the aim of the present project is to evaluate a putative role of SPAG11 isoforms in the modulation of mouse knee joint synovial inflammation and articular cartilage destruction. (AU)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DENADAI-SOUZA, ALEXANDRE; RIBEIRO, CAMILLA MOREIRA; ROLLAND, CORINNE; THOUARD, ANNE; DERAISON, CELINE; SCAVONE, CRISTOFORO; GONZALEZ-DUNIA, DANIEL; VERGNOLLE, NATHALIE; WERNECK AVELLAR, MARIA CHRISTINA. Effect of tryptase inhibition on joint inflammation: a pharmacological and lentivirus-mediated gene transfer study. ARTHRITIS RESEARCH & THERAPY, v. 19, . (12/07784-4, 09/12375-3)
YSHII, LIDIA M.; MANFIOLLI, ADRIANA O.; DENADAI-SOUZA, ALEXANDRE; KINOSHITA, PAULA F.; GOMES, MARCELO D.; SCAVONE, CRISTOFORO. Tumor necrosis factor receptor-associated factor 6 interaction with alpha-synuclein enhances cell death through the Nuclear Factor-kB pathway. IBRO REPORTS, v. 9, p. 218-223, . (12/07784-4, 11/10303-5, 14/24951-7, 09/12375-3, 18/01308-2, 16/07427-8, 19/10044-1, 18/14289-6, 13/22196-4)
YSHII, LIDIA M.; DENADAI-SOUZA, ALEXANDRE; VASCONCELOS, ANDREA R.; AVELLAR, MARIA CHRISTINA W.; SCAVONE, CRISTOFORO. Suppression of MAPK attenuates neuronal cell death induced by activated glia-conditioned medium in alpha-synuclein overexpressing SH-SY5Y cells. JOURNAL OF NEUROINFLAMMATION, v. 12, . (11/10303-5, 11/12255-8, 09/12375-3)
DENADAI-SOUZA, ALEXANDRE; MARTIN, LAURENCE; DE PAULA, MARCO A. VIEIRA; DE AVELLAR, MARIA C. WERNECK; MUSCARA, MARCELO N.; VERGNOLLE, NATHALIE; CENAC, NICOLAS. Role of transient receptor potential vanilloid 4 in rat joint inflammation. ARTHRITIS AND RHEUMATISM, v. 64, n. 6, p. 1848-1858, . (09/12375-3)

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