Investigating the role of fibroblast growth factor 21 (FGF21) as an autophagic inducer during injury and regeneration following hepatic resection associated with ischemia-reperfusion in diabetic and healthy mice.

• Grant number: 16/24992-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2017
• End date: October 31, 2019
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Joilson de Oliveira Martins
• Grantee: Mariana Mendes Braz
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 18/04625-9 - Investigating the role of fibroblast growth factor 21 (FGF21) as an autophagic inducer during injury and regeneration following hepatic resection associated with ischemia-reperfusion in diabetic and healthy mice., BE.EP.PD

Abstract

Introduction: In clinical situations, partial hepatectomy (PH) under ischaemia-reperfusion (I/R) is usually performed to control bleeding during parenchymal dissection. Diabetes is particularly associated with poor prognosis of ischemia reperfusion (I/R) injury. It is well known that I/R significantly reduces liver regeneration after hepatectomy. Fibroblast growth factor 21 (FGF21) is member of the family FGF that comprise a group of 22 proteins which stimulate a wide variety of target cells. FGF21 activate silent mating type information regulator 2 homolog 1 (SIRT1) pathway. SIRT1 plays important roles in the regulation of autophagy. Autophagy during the early phase of liver regeneration may be essential for preserving cellular quality. Aims: we herein propose to examine the generation of FGF21 in diabetic and health mice liver undergoing PH under I/R and the role of FGF21,through the autophagic process, on damage and liver regeneration. We also intended to characterize the influence of FGF21 and SIRT1 modulating against damage and regenerative failure following PH under I/R. Finally, investigate whether adipose tissue as well participate as a source of generation of FGF21 after the submission of the diabetic mice livers to surgical procedure. Methods: Wild (C57BL/6) and diabetics (alloxan, 60mg/kg, i.v.) mice will be undergoing to liver surgery and the effects of different pharmacological treatments on hepatic injury and regeneration, and the underlying mechanisms, will be investigated. As DM is one of the ten diseases that most victimize the world population, increasing knowledge about partial hepatectomy (PH) under ischemia-reperfusion (I/R), including in diabetic subjects, is of fundamental relevance.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MENDES-BRAZ, MARIANA; MARTINS, JOILSON O.. Diabetes Mellitus and Liver Surgery: The Effect of Diabetes on Oxidative Stress and Inflammation. Mediators of Inflammation, 2018. (17/11540-7, 16/24992-0)

MENDES-BRAZ, MARIANA; MARTINS, JOILSON O.. Diabetes Mellitus and Liver Surgery: The Effect of Diabetes on Oxidative Stress and Inflammation. Mediators of Inflammation, v. 2018, p. 11-pg., 2018-01-01. (17/11540-7, 16/24992-0)