Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Biochem Biophys Res Commun. 2013 Sep 6;438(4):640-6. doi: 10.1016/j.bbrc.2013.07.129. Epub 2013 Aug 13.
Prostaglandin E2 (PGE2) is a proinflammatory mediator and activates the canonical Wnt-β-catenin signaling pathway in hematopoietic stem cells. The SZ95 cell line was established from human sebaceous gland cells and is studied as a model system for these cells. Given that 2D culture of SZ95 cells does not recapitulate the organization of sebaceous glands in situ, we developed a 3D culture system for these cells and examined the effects of PGE2 on cell morphology and function.
SZ95 cells maintained in 3D culture formed organoids that mimicked the organization of sebaceous glands in situ, including the establishment of a basement membrane. Organoids exposed to PGE2 were larger and adopted a more complex organization compared with control organoids. PGE2 activated the canonical Wnt signaling pathway as well as increased cell viability and proliferation, mitochondrial metabolism, and lipid synthesis in the organoids.
Culture of SZ95 cells in 3D culture system recapitulates the structure and susceptibility to PGE2 of sebaceous glands in situ and should prove useful for studies of the response of these glands to inflammation and other environmental stressors. Our results also implicate PGE2-induced activation of canonical Wnt signaling pathway in regulation of the morphology,proliferation, and function of "semi-vivo" sebaceous glands.
前列腺素 E2(PGE2)是一种促炎介质,可激活造血干细胞中的经典 Wnt-β-连环蛋白信号通路。SZ95 细胞系源自人类皮脂腺细胞,被研究为这些细胞的模型系统。鉴于 SZ95 细胞的 2D 培养不能重现原位皮脂腺的组织,我们为这些细胞开发了 3D 培养系统,并研究了 PGE2 对细胞形态和功能的影响。
在 3D 培养中维持的 SZ95 细胞形成了类器官,模拟了原位皮脂腺的组织,包括基底膜的建立。与对照类器官相比,暴露于 PGE2 的类器官更大,并且采用更复杂的组织。PGE2 激活了经典的 Wnt 信号通路,并增加了类器官中的细胞活力和增殖、线粒体代谢和脂质合成。
在 3D 培养系统中培养的 SZ95 细胞再现了原位皮脂腺的结构和对 PGE2 的敏感性,应该有助于研究这些腺体对炎症和其他环境应激源的反应。我们的结果还表明,PGE2 诱导的经典 Wnt 信号通路激活参与了“半活体”皮脂腺形态、增殖和功能的调节。