Kidney Week

Abstract: SA-PO137

Role of Sulfotransferase 1C2 in Vitamin D Signaling in Ischemic AKI Associated with Vitamin D Deficiency in Rats

Session Information

• AKI: Metabolism and Cell Death
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• de Braganca, Ana Carolina, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil

Ana Carolina de Braganca, PhD

• Bernardo, Desiree Rita Denelle, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil

Desiree Rita Denelle Bernardo, MS, MSc

• Nascimento, Mariana Moura, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil

Mariana Moura Nascimento, MSc

• dos Santos, Vitor Antonio, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil

Vitor Antonio dos Santos

• Shimizu, Maria HM, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil

Maria HM Shimizu, PhD

• Seguro, Antonio C., Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil

Antonio C. Seguro, MD, PhD

• Canale, Daniele, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil

Daniele Canale, PhD

• Volpini, Rildo A., Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil

Rildo A. Volpini, PhD

• Bacallao, Robert L., Indiana University School of Medicine, Indianapolis, Indiana, United States

Robert L. Bacallao, MD, FASN

• Basile, David P., Indiana University School of Medicine, Indianapolis, Indiana, United States

David P. Basile, PhD

• Viotto, Ana Carolina Rocha, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil

Ana Carolina Rocha Viotto

Background

Cytosolic sulfotransferase enzymes (SULTs) facilitate inactivation/elimination of compounds from the body. SULTs expression is regulated by lipid-/xenobiotic-sensitive receptors, including vitamin D receptor (VDR). SULT1C2 seems to be regulated by vitamin D (VD) status via VDR, and may be an action pathway of VD in mitigating the renal disease progression. Our aim was to study the role of SULT1C2 in VD signaling in ischemic-AKI associated with VD deficiency in rats.

Methods

Male Wistar rats received a VD-depleted diet for 32 days (protocol [P]1-48 h), 37 days (P2–7 days) and 45 days (P3–15 days). Four groups of rats were assigned to each follow-up P: Sham; Renal ischemia/reperfusion (IR); IR with VD deficiency (d+IR); IR with VD replacement (R+IR). During the first 30 days of all P, only the rats in the Sham and IR groups received 40 IU/day of VD (maintenance dose [MD]) orally. On the 30^th day of all P, the rats were submitted to sham or renal ischemia-reperfusion surgeries. On days 30^th and 31^st, VD was administered orally (80 IU/day attack dose) in the Sham, IR and R+IR groups of all P. Once P1 was concluded, the VD MD was offered from the 32^rd day until the end of P2 and 3. We evaluated plasma levels of 25(OH)D, creatinine and cystatin C as well as renal total tissue levels of VDR, immunoblotted for SULT1C2, and kinetic metabolite utilization rates (Biolog assay kit) in mouse S3 proximal tubule cells plus PAPS and SULT1C2 treated with VD.

Results

See figure 1. In vitro studies showed that VD treatment (125 pM-24 h) increased the utilization kinetics of malate, isocitrate, alpha-ketoglutarate, fumarate, and cis-aconitate.

Conclusion

Our study suggests that vitamin D status, via temporal modulation of VDR, regulated the expression of SULT1C2 in the progression of kidney disease after renal ischemia injury. Grants: FAPESP 2022/05519-3, 2022/07409-0, 2019/20840-0.