Study of the interrelationship between the signaling pathways of Klotho and P2X7 receptor in the diabetic nephropathy progression in rats

• Grant number: 14/26750-9
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2015
• End date: February 28, 2018
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Elisa Mieko Suemitsu Higa
• Grantee: Elisa Mieko Suemitsu Higa
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Maria José da Silva Fernandes

Abstract

Diabetic nephropathy (DN) affects about 40% of diabetic patients, being the major cause of morbidity and mortality in this population. Many factors have been described in the pathophysiology of DN including the increase of purinergic receptors expression, in particular P2X7 (P2X7-R), demonstrated recently by our group. The supplementation with N-acetylcysteine antioxidant associated to the practice of aerobic exercises caused substantial improvement of renal function. The P2X7-R plays an important biological role by increasing influx of calcium which results in cell death by apoptosis and/or necrosis. The main agonists of this receptor are composed of extracellular phosphates (ATP). In chronic renal failure there is a mineral metabolism disorder, being the kidney the most important organ for phosphorus excretion; there is evidence that the Klotho protein would participate in such a mechanism by activation of the fibroblast growth factor (FGF-23) that modulates systemic phosphate. So Klotho, which was initially associated with aging, today has been linked to renal chronic diseases, and by acting on phosphorus homeostasis, may play a modulatory role over P2X7-R. The aim of our study is to evaluate the interaction between the Klotho and P2X7-R in the kidney of diabetic rats, and to study the role of both in the DN progression. Diabetes mellitus will be induced with streptozotocin in rats and the expression of the Klotho and P2X7-R proteins will be studied applying up the interference RNA technique. In this method we will alternate the silencing between Klotho and P2X7-R, for the evaluation of the partial absence of one gene about the activation of the other, showing possible interaction about them. (AU)

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)

RODRIGUES, A. M.; SERRALHA, R. S.; LIMA, D. Y.; PUNARO, G. R.; VISONA, I; FERNANDES, M. J. S.; HIGA, E. M. S.. P2X7 siRNA targeted to the kidneys increases klotho and delays the progression of experimental diabetic nephropathy. PURINERGIC SIGNALLING, v. 16, n. 2, MAY 2020. (14/26750-9)