Contribution of AMPK pathway to renal fibrosis and pathogenesis of diabetic nephropathy and retinopathy

• Grant number: 18/25302-3
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): February 01, 2019
• Effective date (End): September 30, 2019
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Jose Butori Lopes de Faria
• Grantee: Gustavo Daniel Campagnaro
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 14/22687-0 - Contribution of AMPK pathway to renal fibrosis and pathogenesis of diabetic nephropathy and retinopathy, AP.TEM

Abstract

Renal fibrosis is the final result of different renal insults. At late stages, it is associated with end stage renal disease (ESRD). Although knowledge on mechanisms involved in the progression of renal disease to fibrosis has advanced significantly treatment and prevention of this condition remain insufficient, since the number of people with ESRD continue to grow. Microvascular chronic complications of diabetes include diabetic nephropathy and retinopathy. Diabetic nephropathy is the leading cause of ESRD worldwide. Diabetic retinopathy is present in roughly 80% of diabetic patients with nephropathy and it is an important cause of blindness in work population. 5' adenosine monophosphate kinase protein activated by AMP (AMPK), is ubiquitous expressed, and it has important role in cellular homeostasis. Although some studies have implicated AMPK into the mechanism of kidney fibrosis, its real contribution to fibrosis in different model of renal diseases deserves further investigation. In DM, it has been proposed that AMPK pathway contributes to the pathogenesis of diabetic nephropathy and retinopathy, however this information is incomplete. Objective of the present study is to investigate the contribution of AMPK pathway in progression to fibrosis in different models of renal diseases, in vivo (diabetes mellitus, unilateral urethral obstruction (UUO), 5/6 renal ablation model) using mice knockout for AMPK, and in vitro (renal cells: podocyte, mesangial, proximal tubular cells and renal fibroblast; retina: glial cells (Müller) and pigmented epithelial cells). The induction of diabetes in AMPK knockout mice should allow investigation on the contribution of this pathway to renal and retina lesions under diabetes. We will also test the efficacy of different drugs that increase AMPK activity on prevention and treatment of different renal diseases and diabetic retinal disease. This will also be tested in presence of renin angiotensin blockade, a maneuver known to reduce progression of renal disease.