Sphingosine 1 phosphate receptor-1 (S1PR1) signaling protects cardiac function by inhibiting cardiomyocyte autophagy.
Sphingosine 1 phosphate receptor-1 (S1PR1) signaling protects cardiac function by inhibiting cardiomyocyte autophagy.
复制标题
鞘氨醇 1 磷酸受体 1 (S1PR1) 信号传导通过抑制心肌细胞自噬来保护心脏功能
DOI：
10.11909/j.issn.1671-5411.2018.05.003
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Liu HB
中科院分区：
文献类型：
--
作者：
Chen YZ;Wang F;Wang HJ;Liu HB
目的探讨1-磷酸鞘氨醇（S1 P）及其受体在心肌细胞自噬、心肌细胞肥大和心功能中的作用。方法分离培养Wistar乳鼠心肌细胞。分别采用饥饿培养和苯肾上腺素（PE）诱导心肌细胞自噬和肥大，并用S1 P处理心肌细胞。通过检测心肌细胞自噬体数量、自噬相关蛋白和自噬标志基因的表达来评价S1 P对心肌细胞自噬的影响。通过检测心肌细胞的表面积和肥大基因的表达来评价S1 P对心肌细胞肥大的影响。随后，使用不同的小干扰RNA（siRNAs）来敲低心肌细胞上的三种类型的S1 P受体的表达，并分析在心肌细胞中介导S1 P信号传导的受体类型。最后，使用Cas9技术在小鼠心肌细胞中敲除鞘氨醇1磷酸受体-1（S1 PR 1）。通过评估心肌细胞自噬、心肌细胞肥大和心脏功能来检查S1 PR 1对心脏自噬和心脏肥大的作用。结果S1 P能显著抑制饥饿诱导的心肌细胞自噬和PE诱导的心肌细胞肥大。结果表明，S1 P处理后，自噬体形成减少，自噬相关蛋白LC 3 II/I及自噬标志基因Atg 5、Atg 12、Beclin 1和LC 3B表达降低。S1 P处理后，心肌细胞表面积减少，肥大基因包括心房钠尿因子（ANF）、骨骼肌和心肌肌动蛋白（SKA）、肌球蛋白重链（β-MHC）和脑钠尿肽（BNP）的表达均减少。与对照组、S1 PR 2和S1 PR 3敲低组相比，S1 PR 1敲低组的心肌细胞自噬和肥大显著增加。在体内，敲除心肌细胞中的S1 PR 1加剧了应激诱导的心脏自噬、心脏肥大和心功能损害。结论S1 P可通过激活S1 PR 1抑制心肌细胞自噬，从而抑制压力超负荷心肌细胞肥大，保护心功能。
Objective To investigate the role of sphingosine-1-phosphate (S1P) and its receptors in cardiomyocyte autophagy, cardiomyocyte hypertrophy and cardiac function. Methods Cardiomyocytes were isolated from neonatal Vista rats. Autophagy and hypertrophy of cardiomyocytes were induced via starvation culture and phenylephrine (PE), respectively, and S1P was used to treat the cardiomyocytes. The effect of S1P on cardiomyocyte autophagy was evaluated by the number of autophagosomes, the expression of autophagy-related proteins and autophagic marker genes in cardiomyocytes. The effect of S1P on cardiomyocyte hypertrophy was evaluated by examining the surface area of cardiomyocytes and the expression of hypertrophic genes. Subsequently, different small interfering RNAs (siRNAs) were used to knockdown the expression of the three types of S1P receptors on cardiomyocytes and to analyze the type of receptor that mediates S1P signaling in cardiomyocytes. Finally, sphingosine 1 phosphate receptor-1 (S1PR1) was knockout in the mouse cardiomyocytes using the Cas9 technique. The effect of S1PR1 on cardiac autophagy and cardiac hypertrophy was examined by assessing cardiomyocyte autophagy, cardiomyocyte hypertrophy and cardiac function. Results Starvation-induced cardiomyocyte autophagy and PE-induced cardiomyocyte hypertrophy were significantly attenuated by S1P. The results showed that the formation of autophagosomes was decreased, the autophagy-associated protein LC3II/I and the expression of autophagic marker genes Atg5, Atg12, Beclin1 and LC3B decreased after S1P treatment. The surface area of the cardiomyocytes was decreased, and the expression of hypertrophic genes, including atrial natriuretic factor (ANF), skeletal muscle and cardiac actin (SKA), myosin heavy chain (β-MHC) and brain natriuretic peptide (BNP) were all decreased after S1P treatment. The autophagy and hypertrophy of cardiomyocytes in the S1PR1 knocked-down group were significantly increased compared to those in the control group, the S1PR2 and the S1PR3 knocked-down groups. In vivo, the knockout of S1PR1 in cardiomyocytes exacerbated stress-induced cardiac autophagy, cardiac hypertrophy and the impairment of cardiac function. Conclusion S1P could inhibit cardiomyocyte autophagy, thereby inhibiting cardiomyocyte hypertrophy and protecting cardiac function by activating S1PR1 in pressure-overloaded cardiomyocytes in mice.
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影响因子：
48
作者：
Mali, Prashant;Esvelt, Kevin M.;Church, George M.
通讯作者：
Church, George M.
影响因子：
5.6
作者：
Ni, Qian;Yuan, Baohong;Yin, Hui
通讯作者：
Yin, Hui
影响因子：
8.8
作者：
Lukomska, A.;Baranowska-Bosiacka, I.;Gutowska, I.
通讯作者：
Gutowska, I.
DOI：
10.1161/atvbaha.117.309326
发表时间：
2018-01
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Chadwick AC;Musunuru K
通讯作者：
Musunuru K
影响因子：
5.6
作者：
Ahmed N;Linardi D;Decimo I;Mehboob R;Gebrie MA;Innamorati G;Luciani GB;Faggian G;Rungatscher A
通讯作者：
Rungatscher A