Thrombospondin-1 and prolyl 4-hydroxylase subunit alpha 3 as potential biomarkers of salivary gland fibrosis.
Thrombospondin-1 and prolyl 4-hydroxylase subunit alpha 3 as potential biomarkers of salivary gland fibrosis.
复制标题
Thrombospondin-1 和脯氨酰 4-羟化酶亚基 α 3 作为唾液腺纤维化的潜在生物标志物
DOI：
10.1016/j.jds.2023.02.009
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发表时间：
2023-07
影响因子：
3.5
通讯作者：
Cao, Yubin
中科院分区：
文献类型：
--
作者：
Zhang, Zijian;Li, Honglin;Wang, Guanru;Zhao, Guile;Li, Chunjie;Cao, Yubin
关键词：
唾液腺纤维化存在于各种生理和病理条件下。本研究旨在通过下一代测序鉴定SG纤维化的新生物标志物。采用排泄总管结扎法建立小鼠SG纤维化模型。下一代测序、差异表达基因（DEG）分析和基因集富集分析通过比较连接和对照SGs。我们使用Cytohubba、分子复合体检测、Lasso逻辑回归和支持向量机算法来识别关键的生物标志物。选择的关键生物标志物通过聚合酶链反应和免疫组织化学进行验证。我们还检索并分析了心、肝、肺和肾纤维化的关键基因表达，以确保SG纤维化关键生物标志物的泛化。结扎后的SGs均可见小叶间和小叶内纤维化，胶原I和转化生长因子β表达改善。新一代测序鉴定出2666个上调的deg和336个下调的deg，这些deg在细胞外基质相关途径中高度富集。多种算法确定了SG纤维化的15个关键生物标志物，包括血栓反应蛋白-1 （THBS1）和脯氨酰4-羟化酶亚单位α 3 （P4HA3）。THBS1和P4HA3的mRNA和蛋白表达在小鼠中得到验证。THBS1在肺和肾纤维化中也高表达，而P4HA3在肝纤维化中表达上调。THBS1和P4HA3可能是SG纤维化的潜在生物标志物。它们也可用于多器官纤维化的诊断。
Fibrosis is present in various physiologic and pathologic conditions of salivary glands (SGs). This study aimed to identify novel biomarkers of SG fibrosis by next-generation sequencing. We established the SG fibrosis mouse model by excretory main duct ligation. Next-generation sequencing, differentially expressed gene (DEG) analysis, and gene set enrichment analysis was performed by comparing ligated and control SGs. We used algorithms of Cytohubba, molecular complex detection, Lasso logistic regression, and support vector machine to identify the key biomarkers. Selected key biomarkers were verified by the polymerase chain reaction and immunohistochemistry. We also retrieved and analyzed the key gene expression in the fibrosis of the heart, liver, lung, and kidney to ensure the generalization of key biomarkers in SG fibrosis. Both interlobular and intralobular fibrosis was confirmed in the ligated SGs, with improved expressions of collagen I and transforming growth factor β. Next-generation sequencing identified 2666 upregulated DEGs and 336 downregulated DEGs, which were highly enriched in the extracellular matrix-related pathways. Multiple algorithms identified 15 key biomarkers in SG fibrosis, including Thrombospondin-1 (THBS1) and Prolyl 4-Hydroxylase Subunit Alpha 3 (P4HA3). The mRNA and protein expression of THBS1 and P4HA3 was verified in mice. THBS1 was also highly expressed in lung and kidney fibrosis, whereas P4HA3 was upregulated in liver fibrosis. THBS1 and P4HA3 may be potential biomarkers for SG fibrosis. They may be also applicable in the diagnosis of multi-organ fibrosis.
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DOI：
10.1016/j.matbio.2018.06.002
发表时间：
2018-10
期刊：
Matrix biology : journal of the International Society for Matrix Biology
影响因子：
--
作者：
Mead TJ;Apte SS
通讯作者：
Apte SS
DOI：
10.1038/labinvest.2010.5
发表时间：
2010-04
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
通讯作者：
--
影响因子：
81.5
作者：
Brito-Zeron, Pilar;Baldini, Chiara;Ramos-Casals, Manuel
通讯作者：
Ramos-Casals, Manuel
影响因子：
4
作者：
Dorotheou D;Farsadaki V;Bochaton-Piallat ML;Giannopoulou C;Halazonetis TD;Kiliaridis S
通讯作者：
Kiliaridis S
影响因子：
7.6
作者：
Yang, N.;Zhang, Q.;Zhang, W.
通讯作者：
Zhang, W.