#4372 TYK2-INDUCED STAT ACTIVATION IS ESSENTIAL FOR VASCULAR PRO-CALCIFIC EFFECTS OF LEUKEMIA INHIBITORY FACTOR

Abstract Background and Aims Hyperphosphatemia in chronic kidney disease (CKD) is closely linked to medial vascular calcification. Phosphate able induce pro-inflammatory effects smooth muscle cells (VSMC), which could actively augment calcification processes. This study investigated the role of IL-6 family member leukemia inhibitory factor (LIF) during Method Experiments were performed primary human aortic VSMCs, ex vivo mouse rings cholecalciferol treated mice, as well serum samples from CKD patients healthy controls. Results exposure induced LIF release while supplementation aggravated expression pro-calcific markers VSMCs. Silencing or addition soluble receptor (LIFR) putative antagonist ameliorated phosphate. Similarly, phosphate blunted by silencing LIFR its coreceptor GP130 Mechanistically, phosphorylation TYK2, was required for STAT1/3 activation. TYK2 overexpression augmented VSMC calcification, either phosphate- LIF-induced markers. Pharmacological inhibition mice after treatment. Furthermore, TYK2-deficient overload. In a pilot study, reduced with levels associated propensity. Conclusion Vascular LIF, identifies crucial reprogramming Inhibition this signalling axis might be reduce burden CKD.