Assessing thioredoxin binding protein (TXNIP) gene influence in zebrafish pancreatic development

• Grant number: 15/22206-5
• Support type: Scholarships abroad - Research Internship - Doctorate (Direct)
• Effective date (Start): April 01, 2016
• Effective date (End): January 31, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal researcher: Mari Cleide Sogayar
• Grantee: Camila Leal Lopes da Silva
• Supervisor abroad: Duc Dong
• Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Research place: Sanford Burnham Prebys Medical Discovery Institute, La Jolla, United States
• Associated to the scholarship: 13/00664-6 - Alternative therapies for T1DM: generation of innovative biomaterials for microencapsulation of islets of Langerhans and clusters from mESCs differentiation and functional analysis of genes differentially expressed, BP.DD

Abstract

Alternative therapies involving cell replacement have raised great expectations for the treatment of type 1 diabetes mellitus (T1D). An interesting alternative therapy for T1D would be the engraftment of insulin-producing cell (IPCs) differentiated from stem cells. Therefore, understanding the mechanisms that lead to pancreas organogenesis lays the foundation for the existence of renewable tissue for diabetic patients' therapy. The protein known as TXNIP (Thioredoxin binding protein) acts as an endogenous negative regulator of Thioredoxin (TRX), decreasing its function as an antioxidant. Regulation of the TRX/TXNIP association has become a therapeutic target for cancer, diabetes and other diseases. TXNIP plays a role regulating transcription factors, which are essential for the pancreatic function, and in the development of pancreatic diseases. Besides, our group has established a differential expression profile for Txnip throughout the differentiation of murine embryonic stem cells into IPCs, supporting the hypothesis that Txnip is crucial for pancreatic organogenesis. In order to elucidate the function of Txnip during pancreas organogenesis and to investigate the fundamental molecular mechanisms which are necessary to obtain viable IPCs, we intend to generate a Txnip knockout in the zebrafish model. This model should allow us to evaluate the role of the Txnip gene not only in pancreatic organogenesis, but, also, in the whole organism, thereby reducing both the time and cost of the in vivo investigation. (AU)