SPHINGOSINE-1-PHOSPHATE AS A POTENTIAL REGULATOR OF RHO GTPASES IN KIDNEY PROXIMAL TUBULE CELLS DURING ISCHEMIA

Gloria M.R.S. Grelle, Teresa C. Calegari-Silva, Pedro Pompeu, Rafael Garrett, Rafael H.F. Valverde and Marcelo Einicker-Lamas*

Kidneys play a crucial role in body homeostasis, and impairing their functions can lead to kidney diseases, including acute kidney injury. There are no effective treatments for these patients; thus, new therapies and the identification of early kidney injury biomarkers are needed to reduce morbidity and mortality. Among the possible biomarkers, bioactive lipids emerge due to their function as important mediators of diverse cellular responses. Sphingosine 1-phosphate (S1P), a bioactive lipid (sphingolipid), acts as an extracellular signaling molecule and an intracellular second messenger that plays a role in several important biological functions related to tissue repair. In this work, we verified the ability of S1P to modulate Rho GTPases, indicating a potential role in the maintenance of cellular polarity through the activation of signaling pathways involved in cytoskeleton assembly/remodeling. In an in vitro ATP depletion injury model, we demonstrated that the Rho GTPases (RhoA, Rac1, and Cdc42) genes and proteins were differentially expressed, affecting their activity in the renal cells used in this study. In addition, the pretreatment of the cells with S1P prevented most of the changes observed for the studied Rho GTPases, which suggests that this bioactive lipid preserved the cell polarity machinery control in vitro. In future studies, we would like to evaluate the amount of S1P and other bioactive lipids that potentially participate in the progression of kidney injury or repair, which would potentially identify new lipidic kidney injury and repair biomarkers, a vital tool for the early detection of prevalent nephropathies.