Potential involvement of S1PR1/STAT3 signaling pathway in cardiac valve damage due to rheumatic heart disease
Potential involvement of S1PR1/STAT3 signaling pathway in cardiac valve damage due to rheumatic heart disease
复制标题
S1PR1/STAT3信号通路可能参与风湿性心脏病引起的心脏瓣膜损伤
DOI：
10.1080/10520295.2019.1574028
复制
发表时间：
2019-08-18
影响因子：
1.6
通讯作者：
Huang, F.
中科院分区：
文献类型：
--
作者：
Wu, X-D;Zeng, Z-Y;Huang, F.
风湿性心脏病（RHD）是发展中国家的一项公共卫生负担。Th17细胞相关细胞因子可能在RHD的发病机制和病情发展中发挥作用，但具体分子机制尚未完全明确。我们研究了1 - 磷酸鞘氨醇受体1（S1PR1）/信号转导及转录激活因子3（STAT3）信号通路在RHD大鼠模型心脏瓣膜损伤中的潜在作用。我们选取20只Lewis大鼠，随机分为对照组和RHD组。通过注射灭活的A组链球菌和完全弗氏佐剂（CFA）构建RHD模型。对照组大鼠注射生理盐水和CFA。采用酶联免疫吸附试验（ELISA）检测Th17细胞相关细胞因子。通过组织学检查评估纤维化情况。运用逆转录 - 定量聚合酶链反应（RT - qPCR）和蛋白质免疫印迹法（western blot）检测S1PR1以及STAT3/磷酸化STAT3（p - STAT3）的表达。在RHD模型中，S1PR1/STAT3信号通路被激活。与对照组相比，RHD组中与Th17细胞相关的白细胞介素 - 17（IL - 17）和白细胞介素 - 21（IL - 21）细胞因子的血清水平显著升高；胶原容积分数也大幅增加。S1PR1/STAT3信号通路可能通过调节Th17细胞参与RHD所致的心脏瓣膜损伤。
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.