Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, NO.169 Donghu Road, Wuhan, 430071, Hubei, China.
BMC Genomics. 2022 Jul 29;23(1):544. doi: 10.1186/s12864-022-08748-6.
Renal inflammation plays a crucial role during the progression of Chronic kidney disease (CKD), but there is limited research on hub genes involved in renal inflammation. Here, we aimed to explore the effects of Annexin A2 (ANXA2), a potential inflammatory regulator, on gene expression in human proximal tubular epithelial (HK2) cells. RNA-sequencing and bioinformatics analysis were performed on ANXA2-knockdown versus control HK2 cells to reveal the differentially expressed genes (DEGs) and regulated alternative splicing events (RASEs). Then the DEGs and RASEs were validated by qRT-PCR.
A total of 220 upregulated and 171 downregulated genes related to ANXA2 knockdown were identified. Genes enriched in inflammatory response pathways, such as interferon-mediated signaling, cytokine-mediated signaling, and nuclear factor κB signaling, were under global transcriptional and alternative splicing regulation by ANXA2 knockdown. qRT-PCR confirmed ANXA2-regulated transcription of chemokine gene CCL5, as well as interferon-regulating genes ISG15, IFI6, IFI44, IFITM1, and IRF7, in addition to alternative splicing of inflammatory genes UBA52, RBCK1, and LITAF.
The present study indicated that ANXA2 plays a role in inflammatory response in HK2 cells that may be mediated via the regulation of transcription and alternative splicing of inflammation-related genes.
肾炎症在慢性肾病（CKD）的进展中起着至关重要的作用，但目前关于参与肾炎症的关键基因的研究有限。在这里，我们旨在探讨膜联蛋白 A2（ANXA2）作为一种潜在的炎症调节因子，对人近端肾小管上皮（HK2）细胞基因表达的影响。对 ANXA2 敲低与对照 HK2 细胞进行 RNA 测序和生物信息学分析，以揭示差异表达基因（DEGs）和调节的可变剪接事件（RASEs）。然后通过 qRT-PCR 验证 DEGs 和 RASEs。
共鉴定出与 ANXA2 敲低相关的 220 个上调基因和 171 个下调基因。基因富集在炎症反应途径中，如干扰素介导的信号转导、细胞因子介导的信号转导和核因子 κB 信号转导，这些途径受到 ANXA2 敲低的全局转录和可变剪接调控。qRT-PCR 证实了 ANXA2 对趋化因子基因 CCL5 的转录调控，以及干扰素调节基因 ISG15、IFI6、IFI44、IFITM1 和 IRF7 的转录调控，此外还对炎症基因 UBA52、RBCK1 和 LITAF 的可变剪接进行了调控。
本研究表明，ANXA2 在 HK2 细胞的炎症反应中发挥作用，可能通过调节炎症相关基因的转录和可变剪接来介导。
