Bone Marrow Mononuclear Cells Administration Restore Lysophosphatidic Acid (LPA) Levels and Cellular Signaling Axis in Rats Submitted to Renal Ischemia-Reperfusion.

Bone marrow-derived mononuclear cells (BMMCs) have shown beneficial effects on tissue repair, largely attributed to the paracrine action of bioactive mediators such as lysophosphatidic acid (LPA). This study aimed to evaluate the effects of BMMC treatment in a rat model of renal ischemia/reperfusion (I/R) injury, focusing on LPA-related molecular pathways. Male Wistar rats were divided into three groups: control; I/R, subjected to bilateral renal artery clamping for 30 min followed by 24 h of reperfusion; and I/R + BMMC, which received 1 × 10 BMMCs per kidney directly into the renal capsule post-ischemia. During reperfusion, the rats were placed in metabolic cages for urine collection, renal function and protein expression. BMMC treatment did not reverse the I/R-induced increase in urine volume or decrease in glomerular filtration rate, serum potassium, or filtered sodium load. However, it prevented proteinuria, increased blood urea nitrogen, and enhanced urinary potassium excretion. Mechanistically, BMMC treatment prevented I/R-induced upregulation of LPAR1, downregulated LPAR2 and LPAR3, restored plasma LPA levels, and reduced renal autotaxin content. These results suggest that BMMCs modulate harmful LPA-related signaling and may contribute to renal protection through paracrine mechanisms in the setting of acute I/R injury.