Background

Psoriasis is a systemic chronic inflammatory skin disorder that was prone to recurrence. The RNA binding protein GNL3 has an important function in maintaining the proliferative ability of stem cells, and its overexpression leads to apoptosis. GNL3 is expressed in the epidermis, however, its regulatory mechanism in psoriasis vulgaris is still poorly understood.

Objective

To identify the role of GNL3 in the pathogenesis of psoriasis vulgaris.

Materials and methods

RNA-seq was performed to obtain the data of genes' expression and splicing events in Hela cells after shGNL3 and shCtrl was transferred. High quality results of differentially expressed genes (DEGs) and alternative splicing events (ASEs) were further attained by quality control and analysis. Through the functional enrichment analysis of DEGs and ASEs, the regulating effect of GNL3 was discussed, and the hypothesis was further confirmed in HaCat cells and psoriasis lesions.

Results

The mRNA expression of IL23A in Hela cells was upregulated in GNL3 knockdown, and the ratio of ASE occurred in TNFAIP3 was increased. However, in HaCaT cells, the mRNA expression level of IL23A was downregulated in GNL3 knockdown, and the ratio of ASE of TNFAIP3 was decreased. Additionally, the results obtained in HaCaT cells was further validated in the lesional psoriatic skin.

Conclusion

GNL3 takes an important part in the development of psoriasis vulgaris by regulating the IL23/IL17 axis, which may serve as the basis of effective targeted treatment in future.

中文翻译：

---

RNA-seq 通过调节 IL23/IL17 轴揭示 RNA 结合蛋白 GNL3 作为寻常型银屑病发展的关键介质

背景

银屑病是一种全身性慢性炎症性皮肤病，容易复发。RNA结合蛋白GNL3在维持干细胞增殖能力方面具有重要作用，其过表达导致细胞凋亡。GNL3在表皮中表达，但其在寻常型银屑病中的调控机制仍知之甚少。

客观的

确定 GNL3 在寻常型银屑病发病机制中的作用。

材料和方法

进行 RNA-seq 以获得转移 shGNL3 和 shCtrl 后 Hela 细胞中基因表达和剪接事件的数据。通过质量控制和分析，进一步获得了差异表达基因 (DEG) 和可变剪接事件 (ASE) 的高质量结果。通过对 DEGs 和 ASEs 的功能富集分析，讨论了 GNL3 的调节作用，并在 HaCat 细胞和银屑病病变中进一步证实了这一假设。

结果

GNL3敲低后Hela细胞中IL23A mRNA表达上调，TNFAIP3中出现ASE的比例增加。然而，在 HaCaT 细胞中，IL23A 的 mRNA 表达水平在 GNL3 敲低时下调，并且 TNFAIP3 的 ASE 比例降低。此外，在 HaCaT 细胞中获得的结果在皮损银屑病皮肤中得到了进一步验证。

结论

GNL3通过调节IL23/IL17轴在寻常型银屑病的发生发展中发挥重要作用，这可能成为未来有效靶向治疗的基础。