Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, 426 Songshi North Road, Yubei District, Chongqing, 401147, China.
Department of Surgery, Laboratory of Craniofacial Biology and Development, Section of Plastic Surgery, The University of Chicago Medical Center, 5841 South Maryland Avenue MC6035, Chicago, IL, 60637, USA.
Cell Mol Biol Lett. 2022 Jun 11;27(1):46. doi: 10.1186/s11658-022-00333-9.
The submandibular gland (SMG) and the sublingual gland (SLG) are two of the three major salivary glands in mammals. In mice, they are adjacent to each other and open into the oral cavity, producing saliva to lubricate the mouth and aid in food digestion. Though salivary gland dysfunction accompanied with fibrosis and metabolic disturbance is common in clinic, in-depth mechanistic research is lacking. Currently, research on how to rescue salivary function is challenging, as it must resort to using terminally differentiated acinar cells or precursor acinar cells with unknown differentiation. In this study, we established reversely immortalized mouse primary SMG cells (iSMGCs) and SLG cells (iSLGCs) on the first postnatal day (P0). The iSMGCs and iSLGCs grew well, exhibited many salivary gland characteristics, and retained the metabolism-related genes derived from the original tissue as demonstrated using transcriptome sequencing (RNA-seq) analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of these two cell lines, which overlapped with those of the SMG and SLG, were enriched in cysteine and methionine metabolism. Furthermore, we investigated the role of bone morphogenetic protein 9 (BMP9), also known as growth differentiation factor 2(Gdf2), on metabolic and fibrotic functions in the SMG and SLG. We demonstrated that iSMGCs and iSLGCs presented promising adipogenic and fibrotic responses upon BMP9/Gdf2 stimulation. Thus, our findings indicate that iSMGCs and iSLGCs faithfully reproduce characteristics of SMG and SLG cells and present a promising prospect for use in future study of salivary gland metabolism and fibrosis upon BMP9/Gdf2 stimulation.
下颌下腺 (SMG) 和舌下腺 (SLG) 是哺乳动物的三大唾液腺中的两个。在小鼠中，它们彼此相邻，开口于口腔，产生唾液以润滑口腔并帮助食物消化。尽管伴有纤维化和代谢紊乱的唾液腺功能障碍在临床上很常见，但深入的机制研究却很缺乏。目前，关于如何挽救唾液腺功能的研究具有挑战性，因为它必须依赖于使用终末分化的腺泡细胞或具有未知分化的前体腺泡细胞。在这项研究中，我们在出生后第 1 天（P0）建立了可反向永生化的小鼠原代 SMG 细胞（iSMGCs）和 SLG 细胞（iSLGCs）。iSMGCs 和 iSLGCs 生长良好，表现出许多唾液腺特征，并保留了源自原始组织的与代谢相关的基因，这一点通过转录组测序（RNA-seq）分析得到了证明。这两种细胞系的京都基因与基因组百科全书（KEGG）途径与 SMG 和 SLG 的途径重叠，富含半胱氨酸和蛋氨酸代谢。此外，我们研究了骨形态发生蛋白 9（BMP9），也称为生长分化因子 2（Gdf2），对 SMG 和 SLG 代谢和纤维化功能的作用。我们证明，iSMGCs 和 iSLGCs 在受到 BMP9/Gdf2 刺激时表现出有前途的成脂和成纤维反应。因此，我们的研究结果表明，iSMGCs 和 iSLGCs 忠实地再现了 SMG 和 SLG 细胞的特征，并为未来研究 BMP9/Gdf2 刺激下的唾液腺代谢和纤维化提供了有前途的前景。
