Ilieva Mirolyuba, Miller Henry E, Agarwal Arav, Paulus Gabriela K, Madsen Jens Hedelund, Bishop Alexander J R, Kauppinen Sakari, Uchida Shizuka
Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, DK-2450 Copenhagen, Denmark.
Department of Cell Systems and Anatomy, UT Health San Antonio, San Antonio, TX 78229, USA.
Noncoding RNA. 2022 Jan 28;8(1):13. doi: 10.3390/ncrna8010013.
Most long non-coding RNAs (lncRNAs) are expressed at lower levels than protein-coding genes and their expression is often restricted to specific cell types, certain time points during development, and various stress and disease conditions, respectively. To revisit this long-held concept, we focused on fibroblasts, a common cell type in various organs and tissues. Using fibroblasts and changes in their expression profiles during fibrosis as a model system, we show that the overall expression level of lncRNA genes is significantly lower than that of protein-coding genes. Furthermore, we identified lncRNA genes whose expression is upregulated during fibrosis. Using dermal fibroblasts as a model, we performed loss-of-function experiments and show that the knockdown of the lncRNAs and result in gene expression changes associated with cellular and inflammatory responses, respectively. Since there are no lncRNA databases focused on fibroblasts and fibrosis, we built a web application, FibroDB, to further promote functional and mechanistic studies of fibrotic lncRNAs.
大多数长链非编码RNA（lncRNA）的表达水平低于蛋白质编码基因，并且它们的表达通常分别局限于特定的细胞类型、发育过程中的特定时间点以及各种应激和疾病状况。为了重新审视这一长期存在的概念，我们聚焦于成纤维细胞，这是各种器官和组织中常见的细胞类型。以成纤维细胞及其在纤维化过程中的表达谱变化作为模型系统，我们发现lncRNA基因的整体表达水平显著低于蛋白质编码基因。此外，我们鉴定出了在纤维化过程中表达上调的lncRNA基因。以皮肤成纤维细胞作为模型，我们进行了功能缺失实验，结果表明lncRNAs和的敲低分别导致了与细胞和炎症反应相关的基因表达变化。由于没有专注于成纤维细胞和纤维化的lncRNA数据库，我们构建了一个网络应用程序FibroDB，以进一步推动对纤维化lncRNA的功能和机制研究。
