摘要
Background: The activation of the epithelial to mesenchymal transition (EMT) program is a pathological response of the Sjögren’s syndrome (SS) salivary glands epithelial cells (SGEC) to chronic inflammation. Follistatin-like 1 protein (FSTL1) is a secreted glycoprotein induced by transforming growth factor-β1 (TGF-β1), actively involved in the modulation of EMT. However, the role of FSTL1 in the EMT program activation in SS has not yet been investigated. Methods: TGF-β1-stimulated healthy human SGEC, SS SGEC, and SS salivary glands (SGs) biopsies were used to assess the effect of FSTL1 on the activation of the EMT program. FSTL1 gene activity was inhibited by the siRNA gene knockdown technique. Results: Here we reported that FSTL1 is up-regulated in SS SGs tissue in a correlated manner with the inflammatory grade. Blockage of FSTL1 gene expression by siRNA negatively modulates the TGF-β1-induced EMT program in vitro. We discovered that these actions were mediated through the modulation of the SMAD2/3-dependent EMT signaling pathway. Conclusions: Our data suggest that the TGF-β1-FSTL1-SMAD2/3 regulatory circuit plays a key role in the regulation of EMT in SS and targeting FSTL1 may be a strategy for the treatment of SGs EMT-dependent fibrosis.
摘要译文
背景：上皮向间质转变（EMT）程序的激活是Sjögren综合征（SS）唾液腺上皮细胞（SGEC）对慢性炎症的病理反应。 follistatin样1蛋白（FSTL1）是通过转化生长因子-β1（TGF-β1）诱导的分泌糖蛋白，积极参与EMT的调节。但是，尚未研究FSTL1在SS中EMT程序激活中的作用。方法：使用TGF-β1刺激健康的人类SGEC，SS SGEC和SS唾液腺（SGS）活检来评估FSTL1对EMT程序激活的影响。 siRNA基因敲低技术抑制了FSTL1基因活性。结果：在这里，我们报告说，FSTL1在SS SGS组织中以与炎症等级相关的方式上调。 siRNA对FSTL1基因表达的阻塞对体外调节TGF-β1诱导的EMT程序。我们发现这些动作是通过SMAD2/3依赖性EMT信号通路的调节来介导的。结论：我们的数据表明，TGF-β1-FSTL1-SMAD2/3调节电路在SS的EMT调节和靶向FSTL1中起关键作用，可能是治疗SGS EMT依赖性纤维化的策略。
Margherita Sisto;Domenico Ribatti;Giuseppe Ingravallo;Sabrina Lisi. The Expression of Follistatin-Like 1 Protein Is Associated with the Activation of the EMT Program in Sjӧgren’s Syndrome[J]. Journal of Clinical Medicine, 2022,11(18): 5368