Factors involved in the regulation of gene expression of antimicrobial gene SPAG11

• Grant number: 11/21546-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2012
• End date: August 31, 2014
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Maria Christina Werneck de Avellar
• Grantee: Renata Marino Romano
• Host Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The epididymides are known for their constant exposure to inflammatory conditions caused or not by bacterial infections, with epididymitis being the fifth cause of genitourinary problems in humans. The identification of antimicrobial genes, such as those encoding beta-defensins, and the analysis of their expression in the male reproductive tract from different species have been important for the understanding of the evolution and function of these defensins in the potential control spread of sexually transmitted diseases and male fertility. Recombinant SPAG11C is known to present potent in vitro antimicrobial activity, with high abundance of expression in the epididymis of adult rats. Based on the fact that the physiological role and the mechanism of action of the isoforms of the SPAG11 gene are not well known and the relevance of these data in the area of andrology, the aim of the present study is to evaluate the impact of different androgenic conditions on posttranscriptional mechanisms involved in the expression of SPAG11 gene transcripts, and to identify and evaluate cis-regulatory elements in the promoter region of this gene by analyzing (1) the stability of Spag11 transcripts, (2) the transcriptional factors involved in the gene regulation of Spag11 by in silico analysis, (3) functional evaluation of the transcriptional factors identified by high-throughput methods of regulatory element discovery, and (4) functional evaluation of the silencing of the genes of transcription factors identified high-throughput methods analysis. The results of the present study will contribute to advance our knowledge about SPAG11 gene regulation and in the better understanding about the mechanisms of innate immunity and defense against pathogens in the male reproductive tract and consequences to male fertility.