Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shanxi, China.
Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan, China.
Aging (Albany NY). 2022 Sep 5;14(17):7052-7064. doi: 10.18632/aging.204271.
To determine the potential diagnostic and therapeutic targets of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS).
We selected the GSE11783, GSE57560 and GSE621 datasets from the GEO database and merged them. R software was used to screen differentially expressed genes (DEGs) between IC/BPS and normal bladder tissues. The "String" online tool is used to analyze DEGs interaction and functional protein enrichment. CIBERSORT online tool was used to analyze the infiltration of immune cells. In addition, we verified the function of BTK in IC/BPS at the clinical samples and cells level.
Bioinformatics analysis revealed that 5 genes were significantly overexpressed in IC/BPS, and the protein-protein interaction diagram showed that BTK was a critical link between these five proteins. At the same time, functional enrichment showed that they were significantly related to innate immunity. Immunoinfiltration showed that mast cell resting in IC/BPS was significantly higher. IHC staining of clinical samples showed that the mast cell markers Tryptase and BTK were highly expressed in IC/BPS tissues. At the cell level, knockdown of BTK inhibited proliferation, migration, invasion, and degranulation of mast cells.
This study provides a new perspective for understanding the molecular mechanisms involved in IC/BPS and suggests that BTK may be a target for treating IC/BPS.
确定间质性膀胱炎/膀胱疼痛综合征(IC/BPS)的潜在诊断和治疗靶点。
我们从 GEO 数据库中选择了 GSE11783、GSE57560 和 GSE621 数据集,并对其进行了合并。使用 R 软件筛选 IC/BPS 和正常膀胱组织之间的差异表达基因(DEGs)。使用“String”在线工具分析 DEGs 相互作用和功能蛋白富集。使用 CIBERSORT 在线工具分析免疫细胞的浸润。此外,我们在临床样本和细胞水平验证了 BTK 在 IC/BPS 中的功能。
生物信息学分析显示,5 个基因在 IC/BPS 中显著过表达,蛋白质-蛋白质相互作用图显示 BTK 是这 5 个蛋白之间的关键环节。同时,功能富集显示它们与固有免疫显著相关。免疫浸润显示 IC/BPS 中的肥大细胞静止明显更高。临床样本的 IHC 染色显示肥大细胞标志物 Tryptase 和 BTK 在 IC/BPS 组织中高度表达。在细胞水平上,BTK 的敲低抑制了肥大细胞的增殖、迁移、侵袭和脱颗粒。
本研究为理解 IC/BPS 中涉及的分子机制提供了新的视角,并表明 BTK 可能是治疗 IC/BPS 的靶点。