ABSTRACT

Rheumatic heart disease (RHD) is a public health burden in developing countries. Th17 cell-associated cytokines might play a role in the pathogenesis and development of RHD, but the specific molecular mechanism is not completely understood. We investigated the potential role of sphingosine-1-phosphate receptor 1 (S1PR1)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in cardiac valve damage in a rat model of RHD. We used 20 Lewis rats divided randomly into control and RHD groups. The RHD model was constructed by injecting inactivated group A Streptococci and complete Freund’s adjuvant (CFA). The rats in the control group were injected with normal saline and CFA. Th17 cell-related cytokines were measured by ELISA. Fibrosis was assessed by histological examination. RT-qPCR and western blot were used to detect the expression of S1PR1 and STAT3/phosphorylated STAT3 (p-STAT3). The S1PR1/STAT3 signaling pathway was activated in the RHD model. Compared to the control group, serum levels of IL-17 and IL-21 cytokines associated with Th17 cells were increased significantly in the RHD group; the collagen volume fraction also was substantially increased. The S1PR1/STAT3 signaling pathway might be involved in RHD induced cardiac valve damage by regulating Th17 cells.