Analysis of alternative events involved in the formation of renal fibrosis in vitamin D deficient rats submitted to nephrectomy 5/6

• Grant number: 18/12297-1
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2018
• End date: November 30, 2020
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Rildo Aparecido Volpini
• Grantee: Rildo Aparecido Volpini
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Ana Carolina de Bragança Viciana ; Antonio Carlos Seguro ; Daniele Canale Cavicchioli ; Maria Heloisa Massola Shimizu

Abstract

In most countries, the incidence and prevalence of chronic kidney disease (CKD) has been increasing over the years. Although there has been a significant improvement in the management of CKD, the disease is still progressive, requiring the application of new protective strategies. Progressive renal fibrosis is present in CKD and involves the participation of several cytokines, including transforming growth factor-²1 (TGF-²1). The mechanisms of renal disease progression and the integration between related molecular pathways remain unknown. It has been shown that the mortality of patients with CKD is directly related to renal function and is associated with traditional risks such as cardiovascular and infections. Increasing evidence shows that vitamin D status may be a non-traditional risk factor for CKD progression. In view of the essential role of vitamin D in renal physiology and mineral homeostasis, we propose to study its effects in an experimental model of CKD already established (nephrectomy 5/6) and analyze alternative pathways involved in the formation of renal fibrosis, including epidermal growth fator receptor (EGFr), in addition to inflammatory pathways and endothelial dysfunction. Wistar rats deficient in vitamin D will undergo 5/6 nephrectomy (Nx) and than we will allocate them into four groups for receiving Losartan, Erlotinib (EGFr inhibitor), Losartan + Erlotinib or no treatment. Animals will be euthanized 60 days after Nx surgery in order to evaluate functional and biochemical parameters. We will collect renal tissue for histomorphological evaluation and for immunohistochemistry and protein expression studies related to pathways of fibrosis formation, inflammation and endothelial dysfunction. (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)

GONCALVES, JANAINA GARCIA; CANALE, DANIELE; DE BRAGANCA, ANA CAROLINA; SEGURO, ANTONIO CARLOS; SHIMIZU, MARIA HELOISA MASSOLA; VOLPINI, RILDO APARECIDO. The Blockade of TACE-Dependent EGF Receptor Activation by Losartan-Erlotinib Combination Attenuates Renal Fibrosis Formation in 5/6-Nephrectomized Rats Under Vitamin D Deficiency. FRONTIERS IN MEDICINE, v. 7, JAN 5 2021. (15/05513-1, 18/12297-1, 18/04930-6)

BERNARDO, DESIREE RITA DENELLE; CANALE, DANIELE; NASCIMENTO, MARIANA MOURA; SHIMIZU, MARIA HELOISA MASSOLA; SEGURO, ANTONIO CARLOS; DE BRAGANCA, ANA CAROLINA; VOLPINI, RILDO APARECIDO. The association between obesity and vitamin D deficiency modifies the progression of kidney disease after ischemia/reperfusion injury. FRONTIERS IN NUTRITION, v. 9, p. 22-pg., 2022-11-17. (18/12297-1, 19/20840-0, 18/04930-6)

NASCIMENTO, MARIANA MOURA; BERNARDO, DESIREE RITA DENELLE; DE BRAGANCA, ANA CAROLINA; MASSOLA SHIMIZU, MARIA HELOISA; SEGURO, ANTONIO CARLOS; VOLPINI, RILDO APARECIDO; CANALE, DANIELE. Treatment with beta-blocker nebivolol ameliorates oxidative stress and endothelial dysfunction in tenofovir-induced nephrotoxicity in rats. FRONTIERS IN MEDICINE, v. 9, p. 15-pg., 2022-08-04. (18/04930-6, 18/12297-1, 19/20840-0)

DOS SANTOS, MICHELE SANTIAGO; CANALE, DANIELE; BERNARDO, DESIREE RITA DENELLE; SHIMIZU, MARIA HELOISA MASSOLA; SEGURO, ANTONIO CARLOS; VOLPINI, RILDO APARECIDO; DE BRAGANCA, ANA CAROLINA. The Restoration of Vitamin D Levels Slows the Progression of Renal Ischemic Injury in Rats Previously Deficient in Vitamin D. FRONTIERS IN MEDICINE, v. 8, APR 1 2021. (18/04930-6, 15/05513-1, 18/12297-1)

BERNARDO, DESIREE; DE BRAGANCA, ANA CAROLINA; MASSOLA SHIMIZU, MARIA HELOISA; SEGURO, ANTONIO CARLOS; NASCIMENTO, MARIANA MOURA; CANALE, DANIELE; VOLPINI, RILDO APARECIDO. OBESITY ASSOCIATED WITH VITAMIN D DEFICIENCY IMPAIRS RENAL FUNCTION, HAEMODYNAMICS, METABOLIC PARAMETERS AND AGGRAVATES THE RENAL MORPHOLOGICAL DAMAGE IN RATS SUBMITTED TO ISCHAEMIA-REPERFUSION INJURY. Nephrology Dialysis Transplantation, v. 37, p. 2-pg., 2022-05-01. (19/20840-0, 18/12297-1, 18/04930-6)

NASCIMENTO, MARIANA MOURA; BERNARDO, DESIREE; DE BRAGANCA, ANA CAROLINA; MASSOLA SHIMIZU, MARIA HELOISA; SEGURO, ANTONIO CARLOS; VOLPINI, RILDO APARECIDO; CANALE, DANIELE. TREATMENT WITH NEBIVOLOL AMELIORATES RENOVASCULAR ALTERATIONS AND OXIDATIVE STRESS IN TENOFOVIR-INDUCED NEPHROTOXICITY IN RATS. Nephrology Dialysis Transplantation, v. 37, p. 2-pg., 2022-05-01. (19/20840-0, 18/12297-1, 18/04930-6)