LINC00707 inhibits myocardial fibrosis and immune disorder in rheumatic heart disease by regulating miR-145-5p/S1PR1

Abstract

ABSTRACT LINC00707 is a lncRNA that can regulate a variety of diseases. This study mainly investigated that the expression of LINC00707 in rheumatic heart disease (RHD) and LINC00707 regulates S1PR1 by targeting miR-145-5p to inhibit myocardial fibrosis and immune disorder in RHD. A rat model of RHD induced by inactivated group A β-hemolytic streptococcus (GSA) was established. Sixty female Lewis rats (8 weeks of age) were randomly divided into six groups, including control (Con), RHD, RHD+NC, RHD+LINC00707, RHD+miR-145-5p and RHD+LINC00707+miR-145-5p. The mRNA expression was detected by Quantitative Real-time polymerase chain reaction (qRT-PCR). Protein expression of S1PR1 was detected by western blot. The levels of myocardial damage markers (CK-MB, cTnl) and inflammatory immune markers (IL-6, IL-17 and IL-21) were measured by enzyme linked immunosorbent assay (ELISA). The Collagen III/I(COLIII/I) ratio, mRNA expression of COLIIIα1 and FSP1 of rat heart valve tissue in the RHD group was observably higher by comparison with the CON group. The expression of LINC00707 was observably lower in the RHD group. LINC00707 inhibited myocardial fibrosis and immune disorder in RHD. MiR-145-5p was the target gene of LINC00707 via Targetscan prediction. Luciferase reporter experiment confirmed that miR-145-5p was directly regulated by LINC00707. The expression of miR-145-5p in the RHD group was observably higher by comparison with the CON group and LINC00707 observably decreased the expression of miR-145-5p. miR-145-5p mimic reversed the inhibiting effect of LINC00707 on myocardial fibrosis and immune disorder. Furthermore, S1PR1 was confirmed to be downstream gene of miR-145-5p and low expressed in the RHD model. LINC00707 could inhibit myocardial fibrosis and immune disorder in RHD by regulating miR-145-5p/S1PR1.