Antimicrobial Spag11 isoforms and interacting partners in the developing rat: identification of gene regulation and potential physiological roles

• Grant number: 09/14649-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): December 01, 2009
• Effective date (End): September 30, 2013
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Maria Christina Werneck de Avellar
• Grantee: Camilla Moreira Ribeiro
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Several genes encoding antimicrobial proteins, including SPAG 11 gene (sperm associated antigen 11), have been reported in the epididymis and other tissues from the male reproductive tract. The SPAG11 gene organization, expression and physiological roles of its protein isoforms, which are abundantly secreted by epithelial cells from the epididymis and tissues from the male reproductive tract, have been recently studied by our group in different species. One goal of our present research line is to focus on the mechanism of action of SPAG11 isoforms. In the present study, the pre- and post-natal developmental pattern of the Spag11 gene (Spag11c and Spag11e; mRNA and protein) will be characterized, using rat as an experimental model. The expression pattern of the androgen receptor (Ar) and three protein partners recently reported to interact with human SPAG11D (full-length and C-terminal region; this C-terminal region also present in rat and human SPAG11E) such as tryptase alpha/beta 1 (Tpsab1), tetraspanin 7 (Tspan7) and attractin (Atrn) will be also analyzed. The potential interaction of SPAG11C (human and rat; full-length and C-terminal region) with these three protein partners will be confirmed. Additionally, the analysis of the promoter region of the rat Spag11 gene, in comparison to other species, will be performed. Real time PCR, in situ hybridization, immunohistochemistry, in silico analysis and proteomic studies will be used. The identification of potential factors involved in Spag11 gene regulation and the mechanism of action of the products of this gene will contribute to a better understand of inflammatory and/or infectious events in the male reproductive tract, and to gain insights into pharmacological tools to be used for the prevention/treatment of sexually transmitted diseases and identification of new therapeutic targets for male fertility.

Scientific publications

(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)

RIBEIRO, CAMILLA M.; QUEIROZ, DANIEL B. C.; PATRAO, MARILIA T. C. C.; DENADAI-SOUZA, ALEXANDRE; ROMANO, RENATA M.; SILVA, ERICK J. R.; AVELLAR, MARIA CHRISTINA W.. Dynamic changes in the spatio-temporal expression of the beta-defensin SPAG11C in the developing rat epididymis and its regulation by androgens. Molecular and Cellular Endocrinology, v. 404, n. C, p. 141-150, MAR 15 2015. (09/14649-3)

RIBEIRO, CAMILLA M.; FERREIRA, LUCAS G. A.; THIMOTEO, DANIEL S.; SMITH, LEE B.; HINTON, BARRY T.; AVELLAR, MARIA CHRISTINA W.. Novel androgen-induced activity of an antimicrobial beta-defensin: Regulation of Wolffian duct morphogenesis. Molecular and Cellular Endocrinology, v. 442, n. C, p. 142-152, FEB 15 2017. (09/14649-3)

RIBEIRO, CAMILLA M.; SILVA, ERICK J. R.; HINTON, BARRY T.; AVELLAR, MARIA CHRISTINA W.. beta-defensins and the epididymis: contrasting influences of prenatal, postnatal, and adult scenarios. ASIAN JOURNAL OF ANDROLOGY, v. 18, n. 2, p. 323-328, MAR-APR 2016. (09/14649-3)