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

Background: 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. Results: 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. Conclusions: 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.