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针对SPHK1/S1P/S1PR2轴可以改善GH分泌的垂体腺瘤的进展

Heng Sun¹, Biao Hu¹, Chunli Wu¹

¹Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Hunan, Changsha, China.

European journal of clinical investigation

|October 27, 2023

概括

阻断神经酶1/神经-1-酸盐/S1P受体2 (SPHK1/S1P/S1PR2) 途径有效地治疗生长激素分泌的垂体腺瘤 (GHPA). 这种方法减少了瘤大小和激素分泌,为GHPA提供了一个新的治疗点.

科学领域:

内分泌学在内分泌学.
在瘤学瘤学.
分子生物学分子生物学

背景情况:

由于治疗效果有限,生长激素分泌的垂体腺瘤 (GHPA) 存在重大健康风险.
在GHPA病变发生过程中,氨酸激酶1 (SphK1) /氨酸-1-酸盐 (S1P) /S1P受体 (S1PRs) 信号传导的作用尚不清楚.
对于有效的GHPA管理,迫切需要新的治疗策略.

研究的目的:

调查SPHK1/S1P信号在GHPA中的病理作用.
评估针对GHPA中S1P受体2 (S1PR2) 途径的治疗潜力.
为了确定GHPA患者的预后生物标志物.

主要方法:

使用了包括生物信息学,功能研究和临床验证在内的综合分析.
在GH3细胞中进行了神素激酶1 (SPHK1) 敲除,以评估其对增殖的影响.
在GHPA模型中评估了S1PR2抑制剂JTE-013的疗效.

主要成果:

在GHPA患者中,SPHK1/S1P信号异常表达,SPHK1倒置抑制细胞增殖.
在GH3细胞中,S1P与S1PR2结合,促进生长激素 (GH) 分泌,同时抑制由Akt-Creb通路介导的亡和自.
服用S1PR2抗剂JTE-013显著减少瘤大小和GH分泌 in vivo.
术前血清S1P水平被确定为GHPA患者预后不佳的生物标志物.

结论:

针对SPHK1/S1P/S1PR2轴为GHPA提供了一个有前途的治疗策略.
抑制S1PR2有效地改善了GHPA的进展.
血清S1P水平可以作为GHPA的有价值的预后指标.

关键词:

JTE-01313 是一个非常好的技术.在S1PR2中使用S1PR2.增长激素分泌的垂体腺瘤斯芬戈辛1酸盐的使用方法

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