Objective
"BACKGROUND
Non–alcoholic steatohepatitis (NASH) is the hepatic event of the metabolic syndrome and is characterized by steatosis and inflammation. Although our understanding of the disease mechanisms has progressed, the therapy options for treatment of NASH remain poor. AMP-activated protein kinase (AMPK) is an important integrator of signals managing energy balance and acts as a protective response to energy stress during metabolic deregulations. Pharmacologic AMPK activation is a well-established treatment strategy against the metabolic syndrome and has been reported to ameliorate steatosis, but accumulating evidence suggests that global AMPK activation is undesirable, especially because of affecting appetite. Macrophage-stimulating protein (MSP) is a multifunctional serum factor secreted from liver cells and a ligand for Recepteur d'origine nantais (RON) receptor tyrosine kinase to initiate downstream signaling pathways in an autocrine fashion. MSP exhibits anti-inflammatory properties on macrophages. Interestingly, MSP-deficient mice on normal diet develop hepatic steatosis. However, the role of MSP in normal liver metabolism and metabolic syndrome remained underexplored. Previous studies by the applicant demonstrated MSP as a negative regulator of hepatic gluconeogenesis and of inflammatory responses, both via AMPK activation.
HYPOTHESIS
MSP-mediated activation of AMPK is an effective treatment option against NASH.
OBJECTIVES
1) Investigate the molecular mechanism and metabolic/anti-inflammatory action of MSP-mediated AMPK activation in cultured hepatocytes and macrophages.
2) Stimulate the MSP/AMPK pathway in liver to assess the potential of ameliorating NASH in relevant mouse models.
DELIVERABLES
1) Identification of novel upstream regulators of AMPK downstream of MSP/RON.
2) Appraisal of MSP for possible treatment of NASH in humans."
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences health sciences nutrition
You need to log in or register to use this function
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2012-IIF
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
6200 MD Maastricht
Netherlands
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.