#3428 DEPLETED HDAC3 ATTENUATES HYPERURICEMIA-INDUCED RENAL INTERSTITIAL FIBROSIS VIA MIR-19B-3P/SF3B3 AXIS

Abstract

Abstract Background and Aims Hyperuricemia (HN) is a threat for the occurrence of renal interstitial fibrosis (RIF). Dysfunctional histone deacetylase 3 (HDAC3) elicit renal fibrosis and damage. This study aimed to explore the role of HDAC3 in HN-induced RIF from microRNA-19b-3p/splicing factor 3b subunit 3 (miR-19b-3p/SF3B3) axis. Method 1. The HN model was established on rats to induce RIF by oral administration of adenine and potassium oxalate; 2. HN rats were injected with related vectors (sh-HDAC3, mimic-miR-19b-3p, sh-HDAC3+miR-19b-3p inhibitor) to suppress and/or promote HDAC3 and/or miR-19b-3p; The detection indicators are listed as follows: (1) Blood samples and urine samples were collected for UA, BUN, Scr and 24 h urine protein measurement; (2) Renal pathological damages, RIF index and renal cell apoptosis were measured by HE, Masson and TUNEL staining; (3) α-SMA, TGF-β1 and FN contents in renal tissues were detected by IHC staining; (4) mRNA and protein levels of HDAC3, miR-19b-3p and SF3B3 in renal tissues were detected by RT-qPCR and/or WB. (5) Interaction of HDAC3 and miR-19b-3p was detected by ChIP and dual luciferase reporter gene assay; (6) Interaction of miR-19b-3p and SF3B3 was predicted/detected by bioinformatics website/dual luciferase reporter gene assay. Results 1. HN induced renal dysfunction, renal pathological damages, RIF and renal cell apoptosis of rats; HN rats showed elevated HDAC3, SF3B3 and reduced miR-19b-3p in renal tissues. 2. Suppressed HDAC3 or promoted miR-19b-3p relieved HN-induced renal dysfunction, renal pathological damages, RIF and renal cell apoptosis; HDAC3 bound to the promoter of miR-19b-3p; miR-19b-3p negatively regulated SF3B3; miR-19b-3p depletion abrogated down-regulated HDAC3-induced effects on HN-induced RIF. Conclusion HDAC3 bound to the promoter of miR-19b-3p to regulate SF3B3. Depressed HDAC3 relived HN-induced RIF by restoring miR-19b-3p and knocking down SF3B3. Targeting HDAC3 and miR-19b-3p/SF3B3 axis may be a promising therapeutic strategy for preventing HN-induced RIF.