PDGFRB as a potential therapeutic target of ankylosing spondylitis: validation following bioinformatics analysis
PDGFRB as a potential therapeutic target of ankylosing spondylitis: validation following bioinformatics analysis
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PDGFRB作为强直性脊柱炎的潜在治疗靶点：生物信息学分析后的验证
DOI：
10.14715/cmb/2020.66.6.23
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发表时间：
2020-01-01
影响因子：
1.6
通讯作者：
Xu, Weidong
中科院分区：
文献类型：
--
作者：
Feng, Xinzhe;Zhu, Shanbang;Xu, Weidong
强直性脊柱炎（AS）是一种慢性、进行性、炎症性疾病，主要累及中轴关节。虽然这种疾病已经有很好的文献记载和研究，但其发病机制仍然没有很好的理解。本研究的目的是筛选和鉴定参与AS进展的关键候选基因。为此，从基因表达综合数据库下载GSE 39340和GSE 41038的表达谱，并以火山图和热图的形式显示。差异表达基因（DEG）通过Limma软件包在R和功能富集分析进行了鉴定。此外，STRING和Cytoscape被用来构建蛋白质-蛋白质相互作用（PPI）网络和筛选重要模块。应用免疫组化技术对AS和正常人滑膜组织进行组织芯片检测，以确定与AS发生相关的主要蛋白质。采用免疫印迹法（WB）和茜素红染色法检测AS成纤维细胞成骨分化过程中血小板源性生长因子受体β（PDGFRB）的表达水平和功能。共筛选出256个DEG，其中上调基因191个，下调基因65个。这些基因的功能主要包括粘附连接、粘着斑和细胞-基质粘附连接。与AS进展最密切相关的通路是TGF-β信号通路、Hippo信号通路和AGE-beta信号通路。此外，免疫组化显示丝裂原活化蛋白激酶1（MAPK 1）、C-X-C基序趋化因子受体4（CXCR 4）和PDGFRB在AS中高表达。发现PDGFRB在成纤维细胞的成骨过程中上调，并刺激AS中的成骨。这些发现可能会提高我们对控制AS的分子机制的理解。PDGFRB的药理学靶向作用可能会抑制AS的骨形成。
Ankylosing spondylitis (AS) is a chronic, progressive, and inflammatory disease that mainly affects the central axis joint. Although this disease has already been well documented and studied, its pathogenesis is still not well understood. This study aimed to screen and identify key candidate genes involved in the progression of AS. For this purpose, expression profiles of GSE39340 and GSE41038 were downloaded from the Gene Expression Omnibus and displayed in the form of volcano plots and heatmaps. Differentially expressed genes (DEGs) were identified by the Limma package in R and functional enrichment analyses were performed. Moreover, STRING and Cytoscape were utilized to construct protein-protein interaction (PPI) networks and screen significant modules. Immunohistol chemistry (IHC) in tissue chips of AS and normal human synovial tissues was performed to confirm the major proteins associated with its development. Western blotting (WB) and alizarin red staining were applied to validate the expression level of platelet-derived growth factor receptor beta (PDGFRB) and function during osteogenesis differentiation of fibroblasts in AS. A total of 256 DEGs were screened, including 191 up-regulated genes and 65 down-regulated genes. The enriched functions of these identified genes mainly included adherens junction, focal adhesion, and cell-substrate adherens junction. The pathways most highly associated with the progression of AS were TGF-beta signaling pathway, the Hippo signaling pathway, and the AGE-RAGE signaling pathway. In addition, IHC showed that mitogen-activated protein kinase 1 (MAPK1), C-X-C motif chemokine receptor 4 (CXCR4), and PDGFRB were highly expressed in AS. PDGFRB was found upregulated during osteogenesis of fibroblasts and stimulates osteogenesis in AS. These findings may improve our understanding of the molecular mechanisms controlling AS. Pharmacological targeting of PDGFRB may initiate a possible suppression of bone formation in AS.