Overexpression of LncRNA AC067945.2 Down-Regulates Collagen Expression in Skin Fibroblasts and Possibly Correlates with the VEGF and Wnt Signalling Pathways
Overexpression of LncRNA AC067945.2 Down-Regulates Collagen Expression in Skin Fibroblasts and Possibly Correlates with the VEGF and Wnt Signalling Pathways
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LncRNA AC067945.2 的过表达会下调皮肤成纤维细胞中的胶原蛋白表达，并可能与 VEGF 和 Wnt 信号通路相关。
DOI：
10.1159/000487167
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Li, Jun
中科院分区：
文献类型：
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作者：
Chen, Ling;Li, Jingyun;Li, Jun
背景/目的：长链非编码RNA（lncRNA）被认为在人类疾病中起着至关重要的作用。然而，lncRNA在增生性瘢痕形成中的功能仍然知之甚少。方法：采用qRT-PCR方法检测AC 067945. 2基因的表达变化。通过瞬时质粒转染在正常皮肤成纤维细胞中进行AC 067945.2的过表达。Western blot检测蛋白表达变化。CCK-8法检测细胞增殖，Annexin V/7-AAD染色检测细胞凋亡。应用mRNA-seq分析AC067945.2过表达细胞中差异表达的mRNA。ELISA法检测VEGF的分泌。结果：AC067945.2在增生性瘢痕组织中表达下调。AC067945.2的过表达不影响细胞增殖，但它温和地促进正常皮肤成纤维细胞的早期凋亡。此外，AC067945.2过表达抑制COL 1A 1、COL 1A 2、COL 3A 1和α-SMA蛋白的表达。转化生长因子-β 1（TGF-β 1）可抑制AC067945.2的表达。基于mRNA-seq数据，与对照组中的mRNA相比，AC067945.2过表达组中有138个mRNA差异表达，包括14个上调和124个下调的转录本。基因本体和途径分析表明，AC067945.2过表达与发育过程，结合，细胞外区域，血管内皮细胞生长因子（VEGF）和Wnt信号通路。ELISA证实AC067945.2过表达可抑制VEGF的分泌。结论：综上所述，我们的数据揭示了一种新的lncRNA AC067945.2的功能，这可能有助于我们理解AC 067945.2在增生性瘢痕形成的发病机制中的调控机制。(C)2018作者（S）由S发布。Karger AG，巴塞尔
Background/Aims: Long non-coding RNAs (lncRNAs) are thought to play crucial roles in human diseases. However, the function of lncRNAs in hypertrophic scar formation remains poorly understood. Methods: Utilizing qRT-PCR, we explored the expression changes of AC067945.2. Overexpression of AC067945.2 in normal skin fibroblasts was performed by transient plasmid transfection. Western blot was used to check the proteins' expression changes. Cell Counting Kit-8 (CCK-8) assay and Annexin V/7-AAD staining were used to examine cell proliferation and apoptosis, respectively. mRNA-seq was applied to dissect the differentially expressed mRNAs in AC067945.2 overexpressed cells. We also performed ELISA to detect the VEGF secretion. Results: AC067945.2 was down-regulated in hypertrophic scar tissues. Overexpression of AC067945.2 did not affect cell proliferation, but it mildly promoted early apoptosis in normal skin fibroblasts. Furthermore, AC067945.2 overexpression inhibited the expression of COL1A1, COL1A2, COL3A1 and alpha-SMA proteins. Transforming growth factor-beta 1 (TGF-beta 1) could inhibit the expression of AC067945.2. Based on mRNA-seq data, compared with mRNAs in the control group, 138 mRNAs were differentially expressed, including 14 up-regulated and 124 down-regulated transcripts, in the AC067945.2 overexpression group. Gene ontology and pathway analyses revealed that AC067945.2 overexpression was correlated with developmental processes, binding, extracellular region, and the vascular endothelial cell growth factor (VEGF) and Wnt signalling pathways. ELISA confirmed that AC067945.2 overexpression could repress VEGF secretion. Conclusion: Taken together, our data uncovered the functions of a novel lncRNA AC067945.2, which might help us understand the mechanisms regulated by AC067945.2 in the pathogenesis of hypertrophic scar formation. (C) 2018 The Author(s) Published by S. Karger AG, Basel