Chemerin-9 stimulates migration in rat cardiac fibroblasts in vitro
Chemerin-9 stimulates migration in rat cardiac fibroblasts in vitro
复制标题
Chemerin-9 刺激大鼠心脏成纤维细胞的体外迁移
DOI：
10.1016/j.ejphar.2021.174566
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发表时间：
2021
影响因子：
5
通讯作者：
Yamawaki Hideyuki
中科院分区：
文献类型：
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作者：
Yamamoto Atsunori;Sagara Ayumi;Otani Kosuke;Okada Muneyoshi;Yamawaki Hideyuki
趋化素是一种脂肪细胞因子，在各种心脏疾病患者血液中浓度升高，可能参与心脏疾病的发病机制。在本研究中，我们研究了趋化素的活性片段趋化素-9对心脏成纤维细胞功能的影响，这些成纤维细胞参与心脏疾病的病理生理。用酶法从成年雄性Wistar大鼠中分离出原代心肌成纤维细胞。用博伊登室法和划痕法测定心脏成纤维细胞的迁移。Western blotting检测Akt和细胞外信号调节激酶（ERK）的磷酸化水平。用2′，7′-二氯二氢氟树脂染色法测定活性氧（ROS）的生成。Chemerin-9显著刺激心肌成纤维细胞迁移。Chemerin-9显著刺激Akt和ERK的磷酸化以及ROS的产生。Akt通路抑制剂LY294002、ERK通路抑制剂PD98059、趋化因子样受体1 （CMKLR1）拮抗剂2-（α-萘ththoyl）乙基三甲基碘化铵或抗氧化剂n-乙酰-l -半胱氨酸可阻止chemerin-9诱导的迁移。综上所述，我们首次发现chemerin-9可能是通过心肌成纤维细胞中CMKLR1介导的ros依赖性Akt和ERK激活来刺激迁移的。有人提出趋化素在心脏疾病的发病机制中起作用。
Since chemerin is an adipocytokine whose concentration in blood increases in the subjects with various cardiac diseases, chemerin may be involved in pathogenesis of cardiac diseases. In the present study, we examined the effects of chemerin-9, an active fragment of chemerin, on functions of cardiac fibroblasts, which are involved in pathophysiology of cardiac diseases. Primary cardiac fibroblasts were enzymatically isolated from adult male Wistar rats. Migration of cardiac fibroblasts was measured by a Boyden chamber assay and a scratch assay. Phosphorylation of Akt and extracellular signal-regulated kinase (ERK) was measured by Western blotting. Reactive oxygen species (ROS) production was measured by 2′,7′-dichlorodihydrofluoresein staining. Chemerin-9 significantly stimulated migration in cardiac fibroblasts. Chemerin-9 significantly stimulated phosphorylation of Akt and ERK as well as ROS production. An Akt pathway inhibitor, LY294002, an ERK pathway inhibitor, PD98059, an antagonist of chemokine-like receptor 1 (CMKLR1), 2-(α-Napththoyl) ethyltrimethylammonium iodide, or an antioxidant, N-acetyl-L-cysteine prevented the migration induced by chemerin-9. In summary, we for the first time revealed that chemerin-9 stimulates migration perhaps through the ROS-dependent activation of Akt and ERK via CMKLR1 in cardiac fibroblasts. It is proposed that chemerin plays a role in the pathogenesis of cardiac diseases.