title: An in vitro culture system for long-term expansion of epithelial and mesenchymal salivary gland cells: role of TGF-β1 in salivary gland epithelial and mesenchymal differentiation.
abstract: Despite a pivotal role in salivary gland development, homeostasis, and disease, the role of salivary gland mesenchyme is not well understood. In this study, we used the Col1a1-GFP mouse model to characterize the salivary gland mesenchyme in vitro and in vivo. The Col1a1-GFP transgene was exclusively expressed in the salivary gland mesenchyme. Ex vivo culture of mixed salivary gland cells in DMEM plus serum medium allowed long-term expansion of salivary gland epithelial and mesenchymal cells. The role of TGF-β1 in salivary gland development and disease is complex. Therefore, we used this in vitro culture system to study the effects of TGF-β1 on salivary gland cell differentiation. TGF-β1 induced the expression of collagen, and inhibited the formation of acini-like structures in close proximity to mesenchymal cells, which adapted a fibroblastic phenotype. In contrast, TGF-βR1 inhibition increased acini genes and fibroblast growth factors (Fgf-7 and Fgf-10), decreased collagen and induced formation of larger, mature acini-like structures. Thus, inhibition of TGF-β signaling may be beneficial for salivary gland differentiation; however, due to differential effects of TGF-β1 in salivary gland epithelial versus mesenchymal cells, selective inhibition is desirable. In conclusion, this mixed salivary gland cell culture system can be used to study epithelial-mesenchymal interactions and the effects of differentiating inducers and inhibitors.
authors.affiliation: Department of Oral Health Sciences, School of Dentistry, University of Washington, Seattle, WA 98195, USA.
authors.forename: Kajohnkiart
authors.initials: K
authors.lastname: Janebodin
authors.forename: Worakanya
authors.initials: W
authors.lastname: Buranaphatthana
authors.forename: Nicholas
authors.initials: N
authors.lastname: Ieronimakis
authors.forename: Aislinn L
authors.initials: AL
authors.lastname: Hays
authors.forename: Morayma
authors.initials: M
authors.lastname: Reyes
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D051526:Fibroblast Growth Factor 10 / Q000096:biosynthesis; D051523:Fibroblast Growth Factor 7 / Q000096:biosynthesis; D018507:Gene Expression Regulation, Developmental; D059630:Mesenchymal Stem Cells; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D012469:Salivary Glands / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; C496464:Fgf10 protein, mouse; C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D053773:Transforming Growth Factor beta1; D051523:Fibroblast Growth Factor 7