Advanced search
Start date

Importance of AMP-activated protein kinase (AMPK) in the regulation of TGF-beta pathway and T regulatory cells differentiation

Grant number: 18/23168-8
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2019
Effective date (End): September 30, 2021
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:José Carlos Farias Alves Filho
Grantee:Cesar Augusto Speck Hernandez
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID


Regulatory T cells (Tregs) play an indispensable role in maintaining immunological tolerance and modulating of chronic inflammatory response. A cytokine TGF-Beta is a crucial mediator in the differentiation of Tregs, once it induces the expression of transcription factor FOXP3, main regulator of genes associated to differentiation of these cells. AMP-Activated Protein Kinase (AMPK) is a sensor of the metabolic state in the cell, and it is activated by the increase of intracellular AMP/ATP ratio. AMPK phosphorylates different proteins that results in the inhibition of anabolic pathways like protein synthesis, while stimulate catabolic pathways such as glycolysis restoring the metabolic equilibrium. Interestingly, AMPK also regulates signaling pathways that are not directly associated with energetic metabolism. In this context, it was demonstrated that in fibroblast, AMPK inhibits the TGF-Beta signaling pathway by phosphorylate proteins of Smads complex, and in that way, to repress the nuclear translocation of complex. In addition, our lab demonstrated recently, that the Hexosamine Biosynthetic Pathway (HBP) was activated by TGF-Beta and play an important role in the differentiation of Tregs induced by this cytokine. It is important to highlight, that the enzyme glutamine: fructose-6-phosphate aminotransferase (GFAT1), enzyme that regulated the flux of HBP from glycolysis, also its phosphorylated and negatively regulated by AMPK. However, the participation of AMPK in the Tregs differentiation it is still not clear. Therefore, this project has as goal to study of AMPK role on the negative control of TGF-Beta pathway and Tregs differentiation. (AU)

News published in Agência FAPESP Newsletter about the scholarship:
Articles published in other media outlets (0 total):
More itemsLess items

Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
HERNANDEZ, Cesar Augusto Speck. Importance of AMP-activated protein kinase (AMPK) in the regulation of TGF-β pathway and T regulatory cells differentiation. 2021. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

Please report errors in scientific publications list by writing to: