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

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2013 Jul 11

PMID 23841093

Citations 23

Authors

Kajohnkiart Janebodin

Worakanya Buranaphatthana

Nicholas Ieronimakis

Aislinn L Hays

Morayma Reyes

Affiliations

Soon will be listed here.

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.

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References

Kratochwil K . Organ specificity in mesenchymal induction demonstrated in the embryonic development of the mammary gland of the mouse. Dev Biol. 1969; 20(1):46-71. DOI: 10.1016/0012-1606(69)90004-9. View

Toida M, Takeuchi J, Hara K, Sobue M, Tsukidate K, Goto K . Histochemical studies of intercellular components of salivary gland tumors with special reference to glycosaminoglycan, laminin and vascular elements. Virchows Arch A Pathol Anat Histopathol. 1984; 403(1):15-26. DOI: 10.1007/BF00689335. View

Kisseleva T, Cong M, Paik Y, Scholten D, Jiang C, Benner C . Myofibroblasts revert to an inactive phenotype during regression of liver fibrosis. Proc Natl Acad Sci U S A. 2012; 109(24):9448-53. PMC: 3386114. DOI: 10.1073/pnas.1201840109. View

Madan A, Kramer B . Immunolocalization of fibroblast growth factor-2 (FGF-2) during embryonic development of the rat submandibular gland. SADJ. 2005; 60(2):58, 60-1. View

Boivin G, OToole B, Orsmby I, Diebold R, Eis M, Doetschman T . Onset and progression of pathological lesions in transforming growth factor-beta 1-deficient mice. Am J Pathol. 1995; 146(1):276-88. PMC: 1870775. View

Higashiyama H, Yoshimoto D, Kaise T, Matsubara S, Fujiwara M, Kikkawa H . Inhibition of activin receptor-like kinase 5 attenuates bleomycin-induced pulmonary fibrosis. Exp Mol Pathol. 2007; 83(1):39-46. DOI: 10.1016/j.yexmp.2006.12.003. View

Ogawa N, Dang H, Lazaridis K, McGuff H, Aufdemorte T, Talal N . Analysis of transforming growth factor beta and other cytokines in autoimmune exocrinopathy (Sjögren's syndrome). J Interferon Cytokine Res. 1995; 15(9):759-67. DOI: 10.1089/jir.1995.15.759. View

Kusafuka K, Yamaguchi A, Kayano T, Takemura T . Immunohistochemical localization of members of the transforming growth factor (TGF)-beta superfamily in normal human salivary glands and pleomorphic adenomas. J Oral Pathol Med. 2001; 30(7):413-20. DOI: 10.1034/j.1600-0714.2001.300706.x. View

Tucker A . Salivary gland development. Semin Cell Dev Biol. 2007; 18(2):237-44. DOI: 10.1016/j.semcdb.2007.01.006. View

10.

Hoffman M, Kidder B, Steinberg Z, Lakhani S, Ho S, Kleinman H . Gene expression profiles of mouse submandibular gland development: FGFR1 regulates branching morphogenesis in vitro through BMP- and FGF-dependent mechanisms. Development. 2002; 129(24):5767-78. DOI: 10.1242/dev.00172. View

11.

Orban P, Chui D, Marth J . Tissue- and site-specific DNA recombination in transgenic mice. Proc Natl Acad Sci U S A. 1992; 89(15):6861-5. PMC: 49604. DOI: 10.1073/pnas.89.15.6861. View

12.

Lombaert I, Brunsting J, Wierenga P, Faber H, Stokman M, Kok T . Rescue of salivary gland function after stem cell transplantation in irradiated glands. PLoS One. 2008; 3(4):e2063. PMC: 2329592. DOI: 10.1371/journal.pone.0002063. View

13.

Dong L, Wang Y, Li S, Yu G, Gan Y, Li D . TGF-beta1 promotes migration and invasion of salivary adenoid cystic carcinoma. J Dent Res. 2011; 90(6):804-9. DOI: 10.1177/0022034511401407. View

14.

Okumura K, Shinohara M, Endo F . Capability of tissue stem cells to organize into salivary rudiments. Stem Cells Int. 2012; 2012:502136. PMC: 3328257. DOI: 10.1155/2012/502136. View

15.

Grygielko E, Martin W, Tweed C, Thornton P, Harling J, Brooks D . Inhibition of gene markers of fibrosis with a novel inhibitor of transforming growth factor-beta type I receptor kinase in puromycin-induced nephritis. J Pharmacol Exp Ther. 2005; 313(3):943-51. DOI: 10.1124/jpet.104.082099. View

16.

Wang J, Chen J, Zhang K, Zhao Y, Nor J, Wu J . TGF-β1 regulates the invasive and metastatic potential of mucoepidermoid carcinoma cells. J Oral Pathol Med. 2011; 40(10):762-8. PMC: 3723136. DOI: 10.1111/j.1600-0714.2011.01051.x. View

17.

McPhee C, Logan M, Freeman M, Baehrecke E . Activation of autophagy during cell death requires the engulfment receptor Draper. Nature. 2010; 465(7301):1093-6. PMC: 2892814. DOI: 10.1038/nature09127. View

18.

Cutler L, Gremski W . Epithelial-mesenchymal interactions in the development of salivary glands. Crit Rev Oral Biol Med. 1991; 2(1):1-12. DOI: 10.1177/10454411910020010101. View

19.

Aigner T, Neureiter D, Volker U, BELKE J, Kirchner T . Epithelial-mesenchymal transdifferentiation and extracellular matrix gene expression in pleomorphic adenomas of the parotid salivary gland. J Pathol. 1999; 186(2):178-85. DOI: 10.1002/(SICI)1096-9896(1998100)186:2<178::AID-PATH161>3.0.CO;2-2. View

20.

Takahashi Y, Nogawa H . Branching morphogenesis of mouse salivary epithelium in basement membrane-like substratum separated from mesenchyme by the membrane filter. Development. 1991; 111(2):327-35. DOI: 10.1242/dev.111.2.327. View