Abstract：
Primary Sjogren\'s Syndrome (pSS) is a chronic autoimmune disease, with unclear pathogenies. Lysine-malonylation (Kmal) as a novel post-translational modification (PTMs) was found associated with metabolic, immune, and inflammatory processes. For purpose of investigating the proteomic profile and functions of kmal in pSS, liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based analysis and bioinformatics analysis are performed based on twenty-eight pSS patients versus twenty-seven healthy controls (HCs). A total of 331 down-regulated proteins and 289 up-regulated proteins are observed in differentially expressed proteins (DEPs) of pSS. We discover the expression of transforming growth factor beta-1 (TGFB1) and CD40 ligand downregulate which enriches in the inflammatory associated pathway. Expression of signal transducer and activator of transcription 1-alpha/beta (STAT1) show upregulation and enrich in type I interferon signaling pathway and IL-27-mediated signaling pathway. In differentially malonylated proteins (DMPs) of pSS, we identify 3 proteins are down-regulated in 7 sites and 18 proteins are up-regulated in 19 sites. Expression of malonylated integrin-linked kinase (ILK) significantly enrich in the focal adhesion pathway. Together, our data provide evidence that downregulation of TGFB1 and CD40LG play a critical role in the inflammatory process of pSS, while upregulation of STAT1 may be associated with IL-27 immunity and pSS immune dysfunction. Moreover, kmal modification at the kinase domain of ILK may destabilize ILK that thus contributing to pSS pathogenies by regulating the focal adhesion pathway. SIGNIFICANCE: Our research offered the first characterization of Kmal, a newly identified form of lysine acylation in pSS, as well as proteomic data on individuals with pSS. In this study, we found that several key DMPs were associated with focal adhesion pathway, which contributes to the development of pSS. The present results provide an informative dataset for the future exploration of Kmal in pSS.
摘要：
原发性干燥综合征(pSS)是一种慢性自身免疫性疾病,病因不明。发现赖氨酸丙二酰(Kmal)作为一种新的翻译后修饰(PTMs)与代谢相关,免疫，和炎症过程。为了研究pSS中kmal的蛋白质组学特征和功能，基于液相色谱-串联质谱（LC-MS/MS）的分析和生物信息学分析是基于28名pSS患者和27名健康对照（HC）进行的。在pSS的差异表达蛋白(DEP)中观察到总共331种下调蛋白和289种上调蛋白。我们发现转化生长因子β-1（TGFB1）和CD40配体的表达下调，从而丰富了炎症相关途径。信号转导和转录激活因子1-α/β（STAT1）的表达在I型干扰素信号通路和IL-27介导的信号通路中表现出上调和富集。在pSS的差异丙二酸化蛋白（DMPs）中，我们发现3个蛋白在7个位点下调，18个蛋白在19个位点上调。丙二酸整合素连接激酶（ILK）的表达显着富集在粘着斑途径中。一起,我们的数据提供了TGFB1和CD40LG的下调在pSS的炎症过程中起关键作用的证据，而STAT1的上调可能与IL-27免疫和pSS免疫功能障碍有关。此外，ILK激酶结构域的kmal修饰可能会使ILK不稳定，从而通过调节粘着斑途径而导致pSS病原体。意义：我们的研究提供了Kmal的第一个特征，在PSS中一种新发现的赖氨酸酰化形式，以及pSS个体的蛋白质组学数据。在这项研究中,我们发现几个关键的DMPs与局灶性粘附途径有关，这有助于PSS的发展。目前的结果为未来在pSS中探索Kmal提供了信息数据集。
