School of Medicine, South China University of Technology, Guangzhou 510006, China.
Guangzhou Key Laboratory of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China.
Int J Mol Sci. 2023 Jun 14;24(12):10116. doi: 10.3390/ijms241210116.
The mechanism of maintaining myometrial contractions during labor remains unclear. Autophagy has been reported to be activated in laboring myometrium, along with the high expression of Golgi reassembly stacking protein 2 (GORASP2), a protein capable of regulating autophagy activation. This study aimed to investigate the role and mechanism of GORASP2 in uterine contractions during labor. Western blot confirmed the increased expression of GORASP2 in laboring myometrium. Furthermore, the knockdown of in primary human myometrial smooth muscle cells (hMSMCs) using siRNA resulted in reduced cell contractility. This phenomenon was independent of the contraction-associated protein and autophagy. Differential mRNAs were analyzed using RNA sequencing. Subsequently, KEGG pathway analysis identified that knockdown suppressed several energy metabolism pathways. Furthermore, reduced ATP levels and aerobic respiration impairment were observed in measuring the oxygen consumption rate (OCR). These findings suggest that GORASP2 is up-regulated in the myometrium during labor and modulates myometrial contractility mainly by maintaining ATP production.
分娩过程中维持子宫收缩的机制尚不清楚。有报道称，在分娩的子宫肌层中激活了自噬，同时高水平表达了能够调节自噬激活的高尔基重组堆积蛋白 2 (GORASP2)。本研究旨在探讨 GORASP2 在分娩过程中子宫收缩中的作用和机制。Western blot 证实了 GORASP2 在分娩子宫肌层中的表达增加。此外，使用 siRNA 敲低原代人子宫平滑肌细胞 (hMSMC) 中的 GORASP2 导致细胞收缩性降低。这种现象与收缩相关蛋白和自噬无关。使用 RNA 测序分析差异表达的 mRNAs。随后，KEGG 通路分析表明，GORASP2 敲低抑制了几个能量代谢途径。此外，在测量耗氧量 (OCR) 时观察到 ATP 水平降低和有氧呼吸受损。这些发现表明，GORASP2 在分娩过程中子宫肌层中上调，并通过维持 ATP 产生来调节子宫肌层的收缩性。
