Department of Dermatology, the Second Affiliated Hospital, The Domestic First-class Discipline Construction Project of Chinese Medicine of Hunan University of Chinese Medicine, Changsha, 410005, Hunan, China.
The Second Clinical College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410005, Hunan, China.
Cell Death Dis. 2021 Jan 15;12(1):86. doi: 10.1038/s41419-020-03305-z.
Psoriasis is a chronic inflammatory disease of the skin with highly complex pathogenesis. In this study, we identified lncRNA SPRR2C (small proline-rich protein 2C) as a hub gene with a critical effect on the pathogenesis of psoriasis and response to treatment using both weighted gene coexpression network analysis (WGCNA) and differential expression analysis. SPRR2C expression was significantly upregulated in both psoriatic lesion samples and HaCaT cell lines in response to IL-22 treatment. After SPRR2C knockdown, IL-22-induced suppression of HaCaT proliferation, changes in the KRT5/14/1/10 protein levels, and suppression of the IL-1β, IL-6, and TNF-α mRNA levels were dramatically reversed. In the coexpression network with SPRR2C based on GSE114286, miR-330 was significantly negatively correlated with SPRR2C, while STAT1 and S100A7 were positively correlated with SPRR2C. By binding to miR-330, SPRR2C competed with STAT1 and S100A7 to counteract miR-330-mediated suppression of STAT1 and S100A7. MiR-330 overexpression also reversed the IL-22-induced changes in HaCaT cell lines; in response to IL-22 treatment, miR-330 inhibition significantly attenuated the effects of SPRR2C knockdown. STAT1 and S100A7 expression was significantly upregulated in psoriatic lesion samples. The expression of miR-330 had a negative correlation with the expression of SPRR2C, while the expression of SPRR2C had a positive correlation with the expression of STAT1 and S100A7. Thus, SPRR2C modulates the IL-22-stimulated HaCaT cell phenotype through the miR-330/STAT1/S100A7 axis. WGCNA might uncover additional biological pathways that are crucial in the pathogenesis and response to the treatment of psoriasis.
银屑病是一种具有高度复杂发病机制的慢性炎症性皮肤病。在这项研究中，我们通过加权基因共表达网络分析（WGCNA）和差异表达分析，确定 lncRNA SPRR2C（小富含脯氨酸蛋白 2C）是一个关键基因，对银屑病的发病机制和对治疗的反应都有重要影响。在 IL-22 处理后，银屑病病变样本和 HaCaT 细胞系中 SPRR2C 的表达均显著上调。在 SPRR2C 敲低后，IL-22 诱导的 HaCaT 增殖抑制、KRT5/14/1/10 蛋白水平的变化以及 IL-1β、IL-6 和 TNF-α mRNA 水平的抑制作用均被显著逆转。在基于 GSE114286 的 SPRR2C 共表达网络中，miR-330 与 SPRR2C 呈显著负相关，而 STAT1 和 S100A7 与 SPRR2C 呈显著正相关。通过与 miR-330 结合，SPRR2C 与 STAT1 和 S100A7 竞争，拮抗 miR-330 对 STAT1 和 S100A7 的抑制作用。miR-330 的过表达也逆转了 HaCaT 细胞系中 IL-22 诱导的变化；在 IL-22 处理下，miR-330 抑制显著减弱了 SPRR2C 敲低的作用。STAT1 和 S100A7 在银屑病病变样本中的表达显著上调。miR-330 的表达与 SPRR2C 的表达呈负相关，而 SPRR2C 的表达与 STAT1 和 S100A7 的表达呈正相关。因此，SPRR2C 通过 miR-330/STAT1/S100A7 轴调节 IL-22 刺激的 HaCaT 细胞表型。WGCNA 可能揭示了银屑病发病机制和对治疗反应中更重要的其他生物学途径。
