Non-Coding RNAs: The New Insight on Hypertrophic Scar

Chen, Ling; Li, Jingyun; Li, Qian; Yan, Hui; Zhou, Bei; Gao, Yanli; Li, Jun

doi:10.1002/jcb.25873

Cited by 40 publications

(30 citation statements)

References 48 publications

(48 reference statements)

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“…Increasing evidence suggests that lncRNAs are involved in the progression of many diseases, including organ fibrosis (26)(27)(28) found that Smad3 induced expression of lncRNA Erbb4-IR, which mediates TGF-b1-induced renal fibrosis. A recent study from our group (31) found that lncRNA AK081284 was involved in the profibrotic effects of IL-17 during cardiac fibrosis in diabetic mice.…”

Section: Discussionmentioning

confidence: 99%

lncRNA PFAL promotes lung fibrosis through CTGF by competitively binding miR‐18a

Shan

et al. 2018

FASEB j.

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Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic parenchymal lung disease of unknown etiology and lacks an effective intervention. Long noncoding RNAs (lncRNAs) participate in organ fibrosis and various pulmonary diseases, but the role of lncRNAs in lung fibrosis is not fully understood. In the present study, we identified that lncRNA NONMMUT021928, designated as pulmonary fibrosis-associated lncRNA (PFAL), was up-regulated in the lungs of mice with experimental lung fibrosis, and in TGF-β1-induced fibrotic lung fibroblasts. Further study showed that overexpression of PFAL promoted cell proliferation, migration, and fibroblast-myofibroblast transition. Overexpression further resulted in extracellular matrix deposition and fibrogenesis in lung fibroblasts through regulation of microRNA-18a (miR-18a). Importantly, knockdown of PFAL alleviated lung fibrosis both in vitro and in vivo. Mechanistically, our study showed that PFAL promoted lung-fibroblast activation and fibrogenesis by acting as a competing endogenous RNA for miR-18a: forced expression of PFAL inhibited the expression and activity of miR-18a, whereas silencing of PFAL had the opposite effect. Furthermore, we found that miR-18a was decreased during lung fibrosis in vitro and in vivo, as well as in patients with IPF. Moreover, knockdown of miR-18a led to fibrogenesis in lung fibroblasts, whereas enhanced expression of miR-18a attenuated TGF-β1-induced lung fibrosis by directly targeting the regulation of connecting tissue growth factor. Taken together, these results revealed the effect and mechanism of lncRNA PFAL in pulmonary fibrosis and suggested that PFAL depletion may provide a novel strategy for the treatment of lung fibrosis.-Li, X., Yu, T., Shan, H., Jiang, H., Sun, J., Zhao, X., Su, W., Yang, L., Shan, H., Liang, H. lncRNA PFAL promotes lung fibrosis through CTGF by competitively binding miR-18a.

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Section: Discussionmentioning

confidence: 99%

lncRNA PFAL promotes lung fibrosis through CTGF by competitively binding miR‐18a

Shan

et al. 2018

FASEB j.

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“…In humans, imbalanced apoptosis and proliferation in HSFs can cause hypertrophic scar formation. The proliferation or apoptosis of hypertrophic scar fibroblasts has been reported to be affected by the non-coding RNAs miR-200b, miR-21 and miR-143-3p [29]. We found that AC067945.2 overexpression slightly promoted early apoptosis in normal skin fibroblasts.…”

Section: Discussionmentioning

confidence: 58%

Overexpression of LncRNA AC067945.2 Down-Regulates Collagen Expression in Skin Fibroblasts and Possibly Correlates with the VEGF and Wnt Signalling Pathways

Chen¹,

Li²,

Li³

et al. 2018

Cell Physiol Biochem

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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 α-SMA proteins. Transforming growth factor-β1 (TGF-β1) 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 upregulated 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

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“…Numerous studies have reported that ncRNAs, including miRNAs and lncRNAs, participate in a variety of basic cellular processes, including ectopic regulation of gene expression, cell proliferation and differentiation, metabolism and apoptosis. With the development of microarray techniques, it has been demonstrated that ncRNAs have a key role in HS ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

Aberrantly expressed long noncoding RNAs in hypertrophic scar fibroblasts in vitro: A microarray study

Huang

et al. 2018

Int J Mol Med

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A hypertrophic scar is the result of abnormal repair of the body after trauma. Histopathologically, it is mostly the result of the excessive proliferation of fibroblasts and the accumulation of extracellular matrix. Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) have a critical role in the regulation of gene expression and in the pathogenesis of diseases. However, the roles of lncRNAs in hypertrophic scars have remained elusive. The present study investigated the profiles of differentially expressed lncRNAs between fibroblasts derived from a hypertrophic scar and normal skin, and explored the possible mechanisms underlying the development of hypertrophic scars. Microarray data indicated that 6,104 lncRNAs and 2,952 mRNAs were differentially expressed. A set of differentially expressed transcripts as confirmed by reverse transcription-quantitative polymerase chain reaction. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to determine the principal functions of the significantly deregulated genes. Furthermore, associated expression networks, including subgroup analysis, competing endogenous RNAs (ceRNAs) and coding-noncoding co-expression networks were constructed using bioinformatics methods. The homology between differentially expressed lncRNAs and mRNAs was assessed and two exon lncRNA were selected to explore their regulatory mechanisms. The ceRNA network inferred that NR_125715 acted as a competing endogenous RNA, bound to microRNA (miR)-141-3p, miR-200a-3p and miR-29 to regulate the expression of the miRs' targets, including transforming growth factor β2 (TGFB2). Similarly, NR_046402 acted as a competing endogenous RNA, which bound to miR-133a-3p.1 and miR-4469 to then regulate the expression of the miRs' targets, including DNA polymerase δ1, catalytic subunit (POLD1). In addition, co-expression analysis indicated that the expression of lncRNAs NR_125715 and NR_046402 was correlated with that of TGFB2 and POLD1 mRNA. The identification of these differentially expressed lncRNAs in the hypertrophic scar-derived fibroblasts in the present study, may provide novel insight into the functional interactions of lncRNA, miRNA and mRNA, and lead to novel theories for the pathogenesis and treatment of hypertrophic scars.

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Non-Coding RNAs: The New Insight on Hypertrophic Scar

Cited by 40 publications

References 48 publications

lncRNA PFAL promotes lung fibrosis through CTGF by competitively binding miR‐18a

lncRNA PFAL promotes lung fibrosis through CTGF by competitively binding miR‐18a

Overexpression of LncRNA AC067945.2 Down-Regulates Collagen Expression in Skin Fibroblasts and Possibly Correlates with the VEGF and Wnt Signalling Pathways

Aberrantly expressed long noncoding RNAs in hypertrophic scar fibroblasts in vitro: A microarray study

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