Effect of BGP-15 in the satellite cell self-renewal

• Grant number: 16/12894-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2016
• End date: August 31, 2017
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Elen Haruka Miyabara
• Grantee: Aline Negromonte dos Santos
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Satellite cells have the capacity to originate differentiated cells, as well as to replenish the quiescent satellite cell pool, a process called self-renewal. In response to the injury of myofibers, satellite cells are activated, proliferate, some of them undergo self-renewal and most of them differentiate into myofibers. Considering that the mechanisms involved in the satellite cell self-renewal process are little known, we hypothesized that the heat shock proteins (HSPs), molecular chaperones involved in several fundamental cellular processes, could participate in the regulation of satellite cell self-renewal. Thus, the use of the drug O- (3-piperidine-2-hydroxy-1-propyl) nicotinic amidoxime (BGP-15), an HSPs inducer, and a hydroxylamine derivative represent a viable strategy to study the influence of HSPs on the process of satellite cell self-renewal. The investigation of this drug is even more attractive because it is able to mitigate the loss of muscle function and to improve muscle structure during the progression of Duchenne muscular dystrophy, it protects against heart failure and atrial fibrillation in mice and it has also been used in clinical trials to attenuate insulin resistance in diabetic patients. Therefore, the objective of this study is to investigate the effect of the in vitro treatment with BGP-15 in the self-renewal of satellite cells from young mice Pax7CreER; R26RYFP (Cre / loxP system, a powerful and innovative technology to trace the fate of satellite cells genetically labeled).