Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, Gainesville, FL 32610, USA.
Oral Biology, University of Florida College of Dentistry, Gainesville, FL 32610, USA.
Int J Mol Sci. 2019 Feb 12;20(3):767. doi: 10.3390/ijms20030767.
Sjögren's syndrome (SjS) is an autoimmune disease that destroys the salivary glands and results in severe dry mouth. Mesenchymal stem cell (MSC) transplantation has been recently proposed as a promising therapy for restoring cells in multiple degenerative diseases. We have recently utilized advanced proteomics biochemical assays to identify the key molecules involved in the mesenchymal-epithelial transition (MET) of co-cultured mouse bone-marrow-derived MSCs mMSCs with primary salivary gland cells. Among the multiple transcription factors (TFs) that were differentially expressed, two major TFs were selected: muscle, intestine, and stomach expression-1 (MIST1) and transcription factor E2a (TCF3). These factors were assessed in the current study for their ability to drive the expression of acinar cell marker, alpha-salivary amylase 1 (AMY1), and ductal cell marker, cytokeratin19 (CK19), in vitro. Overexpression of MIST1-induced AMY1 expression while it had little effect on CK19 expression. In contrast, TCF3 induced neither of those cellular markers. Furthermore, we have identified that mMSCs express muscarinic-type 3 receptor (M3R) mainly in the cytoplasm and aquaporin 5 (AQP5) in the nucleus. While MIST1 did not alter M3R levels in mMSCs, a TCF3 overexpression downregulated M3R expressions in mMSCs. The mechanisms for such differential regulation of glandular markers by these TFs warrant further investigation.
干燥综合征（SjS）是一种自身免疫性疾病，可破坏唾液腺并导致严重的口干。间充质干细胞（MSC）移植最近被提议作为恢复多种退行性疾病中细胞的有前途的治疗方法。我们最近利用先进的蛋白质组学生化测定法，鉴定了与原代唾液腺细胞共培养的鼠骨髓来源间充质干细胞（mMSCs）的间充质上皮转化（MET）相关的关键分子。在差异表达的多个转录因子（TF）中，选择了两个主要的 TF：肌肉、肠和胃表达-1（MIST1）和转录因子 E2a（TCF3）。在当前研究中，评估了这些因素在体外驱动腺细胞标志物α-唾液淀粉酶 1（AMY1）和导管细胞标志物细胞角蛋白 19（CK19）表达的能力。MIST1 的过表达诱导 AMY1 的表达，而对 CK19 的表达几乎没有影响。相比之下，TCF3 既没有诱导这两种细胞标志物的表达。此外，我们已经鉴定出 mMSCs 主要在细胞质中表达毒蕈碱型 3 受体（M3R），在核中表达水通道蛋白 5（AQP5）。虽然 MIST1 没有改变 mMSCs 中的 M3R 水平，但 TCF3 的过表达下调了 mMSCs 中的 M3R 表达。这些 TF 对腺体标志物的这种差异调节的机制需要进一步研究。
