Hou R X, Liu R F, Zhao X C, Jia Y R, An P, Hao Z P, Li J Q, Li X H, Yin G H, Zhang K M
Institute of Dermatology, Taiyuan City Central Hospital, Shanxi Key Laboratory for Immunological Dermatosis, No. 1 Dong San Dao Xiang, Taiyuan, Shanxi, China.
Department of Dermatology, Maternal and Child Care Service Centre of Jinzhong City, Jinzhong, Shanxi, China.
Genet Mol Res. 2016 Sep 2;15(3):gmr8631. doi: 10.4238/gmr.15038631.
Mesenchymal stem cells (MSCs) have pleiotropic immuno-modulatory effects and pro-angiogenic ability, leading to the presumption that MSCs may be involved in the pathogenesis of many inflammatory or autoimmune disorders, including psoriasis. In a previous study, we reported the specific gene expression profile of dermal MSCs from psoriasis. Inflammation- and angiogenesis-related genes, such as lipopolysaccharide-induced tumor necrosis factor-alpha transcription factor (LITAF), dual-specificity protein phosphatase 1 (DUSP1), vascular endothelial growth factor α (VEGFα), and insulin-like growth factor-binding protein-5 (IGFBP5), are abnormally expressed in psoriatic dermal MSCs. As a key regulator of gene expression, miRNA are involved in a wide variety of biological processes; in fact, several miRNAs have been implicated in the development and progression of inflammatory or autoimmune disorders. In this study, we compared the miRNA expression profiles of dermal MSCs from patients with psoriasis to those in MSCs from normal individuals by microarray, and found that the pro-inflammatory miRNA miR-155 was significantly overexpressed in psoriatic MSCs (2.44 fold, P < 0.001). Additionally, the expression of miR-155 target gene TAB2 (8.47 ± 1.55 vs 6.38 ± 2.10, P < 0.01,) and the downstream gene iNOS (5.26 ± 2.58 vs 3.73 ± 1.89, P < 0.05) was found to be inhibited in psoriatic dermal MSCs by real-time PCR. Therefore, we speculated that the elevation in miR-155 levels may be an indicator of, or a key regulatory pathway in, the pathogenesis of psoriasis, resulting in functionally impaired dermal MSCs.
间充质干细胞(MSCs)具有多效性免疫调节作用和促血管生成能力,这使得人们推测MSCs可能参与了包括银屑病在内的许多炎症性或自身免疫性疾病的发病机制。在先前的一项研究中,我们报道了银屑病患者皮肤MSCs的特定基因表达谱。炎症和血管生成相关基因,如脂多糖诱导的肿瘤坏死因子-α转录因子(LITAF)、双特异性蛋白磷酸酶1(DUSP1)、血管内皮生长因子α(VEGFα)和胰岛素样生长因子结合蛋白5(IGFBP5),在银屑病皮肤MSCs中异常表达。作为基因表达的关键调节因子,miRNA参与了多种生物学过程;事实上,几种miRNA已被证明与炎症性或自身免疫性疾病的发生和发展有关。在本研究中,我们通过微阵列比较了银屑病患者皮肤MSCs与正常个体MSCs的miRNA表达谱,发现促炎miRNA miR-155在银屑病MSCs中显著上调(2.44倍,P < 0.001)。此外,通过实时PCR发现,miR-155靶基因TAB2(8.47 ± 1.55对6.38 ± 2.10,P < 0.01)和下游基因iNOS(5.26 ± 2.58对3.73 ± 1.89,P < 0.05)的表达在银屑病皮肤MSCs中受到抑制。因此,我们推测miR-155水平的升高可能是银屑病发病机制的一个指标或关键调节途径,导致皮肤MSCs功能受损。