#6679 ANALYSIS OF MACROPHAGE POPULATIONS IN THE KIDNEY WITH RENAL TUBULAR CELL-SPECIFIC SENESCENCE INDUCTION

Abstract Background and Aims Ageing is a risk factor for multiple diseases, including kidney disease. To improve quality of life, pharmaceutical treatments are given to ageing patients, often with side-effects cross-reactions. Research needed into the effects mechanisms in order identify new druggable targets life. Cells can become senescent age seen at sites tissue injury. Senescent cells (SCs) undergo irreversible cell-cycle arrest, but remain metabolically active, producing range signalling molecules called senescence associated secretory phenotype (SASP, made up pro-inflammatory/fibrotic elements). within post-acute injury (AKI) may be involved ongoing damage, leading some cases chronic disease (CKD), possibly due interactions macrophages. We hypothesise that recruitment monocytes/macrophages by components present their SASP. Method Pax8 renal tubule marker. use Pax8-creERT2;mdm2 fl/fl mice study kidney-specific induction absence age/injury. Upon administration tamoxifen, mdm2 alleles floxxed out cre recombinase, allowing p53 stabilise activate p21CIP1 inhibitor, inducing Pax8+ cells. The an endogenous tdTomato reporter allows visualisation undergoing successful recombination upon tamoxifen (TAM). Results As expected, inhibitor/SC marker, Cdkn1a was upregulated qPCR TAM-treated young murine whole kidneys 10-fold compared controls (p = 0.0173) (Figure 1). Ccl2 (monocyte chemoattractant) up-regulated 20-fold 0.0405) TG vs In agreement increase transcripts, there significant macrophages as quantified flow cytometry digests 0.0141) TAM treated mice. Immunofluorescence staining transgenic revealed Iba1 positive macrophages, correlated tubules, suggesting macrophage numbers response 2). Iba1-p21 co-stains show increases p21 mice, evidently result construct activation appear proximity Conclusion Apparent presence indicate one which AKI progresses CKD, particularly if inflammatory phenotypes persist. Macrophage monocyte populations fluctuate this model analysis recruitment/polarisation cell burden age/injury possible confounding factors,