Three-dimensional culture of sebaceous gland cells revealing the role of prostaglandin E2-induced activation of canonical Wnt signaling

• Published in: Biochemical and biophysical research communications 2013-09, Vol.438 (4), p.640-646
• Main Authors: Yoshida, Go J., Saya, Hideyuki
• Format: Article
• Language: English
• Subjects: 3D culture; Animals; Canonical Wnt signaling; CD44 variant; Cell Culture Techniques; Cell Line; Dinoprostone - immunology; Humans; Lipid Metabolism; Lipids - immunology; Mice; Mitochondria - immunology; Mitochondria - metabolism; Organoid; Organoids - cytology; Organoids - immunology; Organoids - metabolism; Prostaglandin E2; Sebaceous gland; Sebaceous Glands - cytology; Wnt Signaling Pathway
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2013.07.129

•Three-dimensional culture generates “semi-vivo” sebaceous glands.•Xenograft model failed to mimic the biology of sebaceous glands in vivo.•Proinflammatory cytokine PGE2 enhances Wnt signal activity in the organoids.•PGE2 influences on the mitochondrial and lipid metabolism in the organoids.•Considering 3R agenda, “semi-vivo” sebaceous glands are useful for research. 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.