#2685 SLC34A2 EXACERBATES TUBULAR INTERSTITIAL FIBROSIS VIA INDUCTION OF APOPTOSIS AND CELL CYCLE ARREST IN S PHASE

Abstract Background and Aims Chronic kidney disease (CKD) is an urgent public health issue in the world. However, effective treatments for intervention of CKD remain undefined. Phosphate (Pi) essential element synthesis DNA, RNA, ATP, phospholipid membranes, regulation phosphorylation/dephosphorylation, cellular signaling metabolic pathways. Solute carrier family 34 (SLC34) responsible Pi absorption small intestine. role SLC34 progression still unknown. Method A membrane protein, solute member 2 (SLC34A2), was discovered by using big data mining from National Center Biotechnology Information (NCBI). SLC34A2 overexpressed human proximal tubular cells, HK-2, Lipofectamine 3000. RNA sequencing carried out to uncover SLC34A2-mediated pathways Illumina platform. Apoptosis evaluated Annexin V-PI staining TEUNEL assay cells mouse kidneys, respectively. Cell cycle measured flow cytometry. Unilateral ureteral obstruction (UUO) bilateral renal ischemia-reperfusion injury (bIRI) were employed generate models. Results By NCBI, we identified a SLC34A2, upregulated various types nephropathies including diabetic nephropathy, focal segmental glomerulosclerosis, minimal change disease, ANCA-associated vasculitis. Overexpression suppressed viability HK-2 cells. revealed that apoptosis cell are high scored modulated SLC34A2. The results further verified Ectopic promoted via downregulation BCL-2. Moreover, induced arrest S phase CDK2. models UUO bIRI confirm vitro findings. In mice expression Slc34a2 groups superior sham groups. Enriched Bax TUNEL-positive observed fibrotic kidneys mice. increased p21 downregulated Cyclin A2 confirmed phase. Conclusion halted phase, resulting subsequent tubulointerstitial fibrosis Our suggest targeting might be promising strategy CKD.