Horiuchi A, Nikaido T, Ya-Li Z, Ito K, Orii A, Fujii S
Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Japan.
Mol Hum Reprod. 1999 Feb;5(2):139-45. doi: 10.1093/molehr/5.2.139.
Mast cells are widely distributed in human tissues, including the human uterus. However, the function of mast cells in uterine smooth muscle has not been clearly established. Mast cells possess secretory granules containing such substances as heparin, serotonin, histamine and many cytokines. To help establish the role of mast cells in the human myometrium, the action of heparin was investigated using smooth muscle cells (SMC) from normal myometrium and from leiomyoma. The proliferation of cultured myometrial and leiomyomal SMC was inhibited by heparin treatment. Flow cytometric analysis showed that the population in the G1 phase of the cell cycle increased under heparin treatment. Western blotting analysis showed that markers of SMC differentiation such as alpha-smooth muscle actin (alpha-SMA), calponin h1 and cyclin-dependent kinase inhibitor p27 were induced by heparin, whereas cell-cycle-related gene products from the G1 phase of the cell cycle, such as cyclin E and cdk2, were not changed. Taken together, these results indicate that heparin inhibits the proliferation of myometrial and leiomyomal SMC through the induction of alpha-SMA, calponin h1 and p27. We suggest that heparin from mast cells may induce differentiation in uterine SMC and may influence tissue remodelling and reconstruction during physiological and pathophysiological events.
肥大细胞广泛分布于人体组织中，包括人体子宫。然而，肥大细胞在子宫平滑肌中的功能尚未明确。肥大细胞含有分泌颗粒，其中包含肝素、5-羟色胺、组胺和许多细胞因子等物质。为了帮助确定肥大细胞在人子宫肌层中的作用，利用来自正常子宫肌层和平滑肌瘤的平滑肌细胞（SMC）研究了肝素的作用。肝素处理可抑制培养的子宫肌层和平滑肌瘤SMC的增殖。流式细胞术分析表明，在肝素处理下，细胞周期G1期的细胞群体增加。蛋白质印迹分析表明，肝素可诱导SMC分化标志物，如α-平滑肌肌动蛋白（α-SMA）、钙调蛋白h1和细胞周期蛋白依赖性激酶抑制剂p27，而细胞周期G1期的细胞周期相关基因产物，如细胞周期蛋白E和细胞周期蛋白依赖性激酶2（cdk2）则未发生变化。综上所述，这些结果表明，肝素通过诱导α-SMA、钙调蛋白h1和p27来抑制子宫肌层和平滑肌瘤SMC的增殖。我们认为，肥大细胞产生的肝素可能诱导子宫SMC分化，并可能在生理和病理生理过程中影响组织重塑和重建。
