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

• Grant number: 14/22687-0
• Support Opportunities: Research Projects - Thematic Grants
• Duration: September 01, 2015 - February 28, 2022
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Jose Butori Lopes de Faria
• Grantee: Jose Butori Lopes de Faria
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Clarice Kazue Fujihara ; Jacqueline Mendonça Lopes de Faria ; William Tadeu Lara Festuccia
• Associated scholarship(s): 21/00756-4 - Contribution of irisin / AMPK to renal fibrosis in diabetes mellitus: an in vitro study, BP.TT; 20/14717-8 - Does the elevation of irisin induced by physical exercise contribute to renal protection in experimental Diabetes?, BP.IC; 20/01188-7 - AMPK pathway contribution to renal fibrosis and pathogenesis of Diabetic Nefropathy and Retinopathy, BP.PD; + associated scholarships 19/25491-3 - The contribution of AMPK pathway to renal fibrosis and pathogenesis of diabetic nephro and retinopathy., BP.TT; 19/07197-0 - The contribution of AMPK pathway to renal fibrosis and pathogenesis of diabetic nephro and retinopathy., BP.TT; 18/25302-3 - Contribution of AMPK pathway to renal fibrosis and pathogenesis of diabetic nephropathy and retinopathy, BP.PD; 18/25398-0 - The contribution of AMPK pathway to renal fibrosis and pathogenesis of diabetic nephro and retinopathy., BP.TT; 18/13726-3 - The contribution of AMPK pathway to renal fibrosis and pathogenesis of diabetic nephro and retinopathy., BP.TT; 18/08203-1 - The contribution of AMPK pathway to renal fibrosis and pathogenesis of diabetic nephro and retinopathy, BP.TT; 16/14519-6 - Contribution of AMPK via Rheb/mTORC1 for the renal fibrosis mechanism, BP.IC; 15/22825-7 - Contribution of AMPK pathway to renal fibrosis and pathogenesis of diabetic nephropathy and retinopathy, BP.PD; 15/23258-9 - The role of AMPK in the neural-retina and blood-retinal barrier in a model of experimental diabetes in mice knockout for AMPKalpha-1 and AMPKalpha-2. New perspective in the pharmacological treatment of diabetic retinopathy, BP.PD - associated scholarships

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. (AU)

Scientific publications

(6)

(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)

BORGES, CYNTHIA M.; FUJIHARA, CLARICE KAZUE; MALHEIROS, DENISE M. A. C.; DE AVILA, VICTOR FERREIRA; FORMIGARI, GUILHERME PEDROM; LOPES DE FARIA, JOSE B.. Metformin arrests the progression of established kidney disease in the subtotal nephrectomy model of chronic kidney disease. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, v. 318, n. 5, p. F1229-F1236, MAY 2020. (14/22687-0)

DATILO, MARCELLA N.; FORMIGARI, GUILHERME P.; LOPES DE FARIA, JOSE B.; LOPES DE FARIA, JACQUELINE M.. AMP kinase activation by Omega-3 polyunsaturated fatty acid protects the retina against ischemic insult: An in vitro and in vivo study. EXPERIMENTAL EYE RESEARCH, v. 226, p. 10-pg., 2022-12-18. (14/22687-0, 18/07398-3)

ANGÉLICA MOISES ARTHUR; RANGEL ARTHUR; ALEXANDRE GONÇALVES SILVA; MARINA SILVA FOUTO; YUZO IANO; JACQUELINE MENDONÇA LOPES DE FARIA. Algorithm for predicting macular dysfunction based on moment invariants classification of the foveal avascular zone in functional retinal images. Res. Biomed. Eng., v. 33, n. 4, p. 344-351, 2017-12-21. (14/22687-0)

DATILO, M. N.; FORMIGARI, G. P.; LOPES DE FARIA, J. B.; LOPES DE FARIA, J. M.. The role of AMPK in the mechanism of ischaemic retinopathy: an in vitro study. Diabetologia, v. 63, n. SUPPL 1, p. 2-pg., 2020-09-01. (18/07398-3, 16/16655-4, 14/22687-0)

. Algorithm for predicting macular dysfunction based on moment invariants classification of the foveal avascular zone in functional retinal images. Res. Biomed. Eng., n. ahead, p. -, 2017. (14/22687-0)

BORGES, CYNTHIA M.; PAPADIMITRIOU, ALEXANDROS; DUARTE, DIEGO A.; DE FARIA, JACQUELINE M. LOPES; DE FARIA, JOSE B. LOPES. The use of green tea polyphenols for treating residual albuminuria in diabetic nephropathy: A double-blind randomised clinical trial. SCIENTIFIC REPORTS, v. 6, JUN 20 2016. (08/57560-0, 14/22687-0)