Analysis of complement system action on micro RNAs expression in systemic loxoscelism

• Grant number: 16/10613-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2016
• End date: March 21, 2017
• Field of knowledge: Biological Sciences - Immunology - Immunochemistry
• Principal Investigator: Denise Vilarinho Tambourgi
• Grantee: Paola Fernanda Fedatto
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling, AP.CEPID

Abstract

Analysis of complement system action in microRNAs expression in systemic loxoscelismABSTRACTRenal failure is one of the major causes of death after Loxosceles spider envenomation, and recently we have started to investigate the mechanism of renal dysfunction induced by Loxosceles venom. Complement activation is implicated in ischaemic renal injury and our preliminary experiments using C6-deficient mice suggest that in the case of systemic loxoscelism, complement activation also contributes to the pathology. The discovery and characterization of microRNAs (miRs), a class of non-coding RNAs, is revolutionizing our understanding of gene regulation, cell differentiation, proliferation, apoptosis, metabolism and pathophysiology of many diseases including kidney diseases. miRs have been described as molecules released into the circulation during polymicrobial sepsis, functioning as a mediator to promote extracellular activation of the complement system. Understanding the molecular disturbances of complement system and miR caused by envenomation Loxosceles can open the field for a new class of therapeutic agents to minimize the damage. Thus, in this project we propose to evaluate the expression of modulated miRs by SMase D in the absence and presence of complement system or inhibitors in human kidney cell line HK -2 and culture supernatant; verify the in vitro effects of ectopic expression or inhibition of certain modulated miRs emphasizing the processes of cell viability and pro- or anti-inflammatory. Moreover, we also aim to assess the influence of some miRs selected for resistance and sensitization to treatment with complement inhibitors in the HK-2 cell line. MiRs that result in significant responses in vitro assays will be used to conduct future experiments in vivo to allow study the therapeutic potential of miRNA in systemic loxocelism. (AU)