Role of sulfotransferase 1C2 in vitamin D signaling in a murine ischemic-AKI model

• Grant number: 22/05519-3
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2023
• End date: May 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Ana Carolina de Bragança Viciana
• Grantee: Ana Carolina de Bragança Viciana
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Antonio Carlos Seguro ; Daniele Canale Cavicchioli ; Janaína Garcia Gonçalves ; Maria Heloisa Massola Shimizu ; Rildo Aparecido Volpini

Abstract

Acute kidney injury (AKI) associated with vitamin D deficiency (VDD) potentiates the injury and may accelerate the renal disease progression (RDP). On the other hand, we demonstrated that vitamin D replacement in ischemic-AKI associated with VDD mitigated the RDP. Cytosolic sulfotransferase enzymes (SULTs) regulate the synthesis and biological activity of various hormones, in addition to participating in the body's detoxification process. The expression of SULTs is regulated by lipid- and xenobiotic-sensitive receptors, including vitamin D receptor (VDR). Specifically, sulfotransferase 1C2 (SULT1C2) seems to be regulated by vitamin D status via VDR, and may be a pathway of action of vitamin D in mitigating the RDP. Objective: Our aim is to study the participation of sulfotransferase 1C2 (SULT1C2) in vitamin D signaling in ischemic-AKI associated with VDD in rats. Materials and Methods: Male Wistar rats (180-200 g) will receive a vitamin D-depleted diet for 32 days (protocol 1), 37 days (protocol 2) and 45 days (protocol 3). Four groups of rats will be assigned to each follow-up protocol: Sham (Control); Renal ischemia/reperfusion (I/R); Renal ischemia/reperfusion with vitamin D deficiency (I/R dVD); and Renal ischemia/reperfusion with vitamin D replacement (I/R RVD). During the first 30 days of all protocols, only the animals in the Control and I/R groups will receive 40 IU/day of vitamin D (maintenance dose) orally (VO). On the 30th day of all protocols, the animals will be submitted to sham or renal ischemia-reperfusion surgeries. Right after the surgeries, on the first two days (31st and 32nd), vitamin D will be administered orally at a concentration of 80 IU/day (attack dose) for the rats in the Control, I/R and I/R RVD groups of protocols 1, 2 and 3. Once protocol 1 is concluded, the maintenance dose of vitamin D will be offered from the 33rd day until the end of protocols 2 and 3. ELISA, western blot, qPCR and immunohistochemistry experiments will be performed to evaluate the participation of SULT1C2, renal injury pathways, cytochrome P450, sulfonation of SULTs and the formation of the RXR-VDR heterodimer. (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)

DE BRAGANCA, ANA CAROLINA; BERNARDO, DESIREE RITA DENELLE; NASCIMENTO, MARIANA MOURA; DOS SANTOS, VITOR ANTONIO; SHIMIZU, MARIA H. M.; SEGURO, ANTONIO C.; CANALE, DANIELE; VOLPINI, RILDO A.; BACALLAO, ROBERT L.; BASILE, DAVID P.; et al. Role of Sulfotransferase 1C2 in Vitamin D Signaling in Ischemic AKI Associated with Vitamin D Deficiency in Rats. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, v. 35, n. 10, p. 2-pg., 2024-10-01. (22/05519-3, 19/20840-0, 22/07409-0)