Bromfenac Inhibits TGF-β1–Induced Fibrotic Effects in Human Pterygium and Conjunctival Fibroblasts

Chen, Kailin; Lai, Kairan; Zhang, Xiaobo; Qin, Zhenwei; Fu, Qiang; Luo, Chenqi; Jin, Xiuming; Hu, Jianghua; Liu, Siyu; Yao, Ke

doi:10.1167/iovs.18-24743

Cited by 13 publications

(9 citation statements)

References 49 publications

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“… 44 – 46 Besides, impression cytology specimens of pterygium show fewer apoptotic markers, and PI3K-Akt inhibitor has been proved to reduce the TGF-β-induced synthesis of FN in human pterygium fibroblasts. 47 Moreover, our GSEA-based GO analysis confirmed keratinization and cornification pathway participated in the pathogenesis of pterygium. Previous reports have confirmed that the expression of keratin markers is upregulated in the epithelium of pterygium, and takes effect in the epithelial abnormal differentiation.…”

Section: Discussionmentioning

confidence: 59%

Exploring the Molecular Mechanisms of Pterygium by Constructing lncRNA–miRNA–mRNA Regulatory Network

Cui

Dong

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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This research explores the aberrant expression of the long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) in pterygium. A competitive endogenous RNA (ceRNA) network was constructed to elucidate the molecular mechanisms in pterygium. METHODS. We obtained the differentially expressed mRNAs based on three datasets (GSE2513, GSE51995, and GSE83627), and summarized the differentially expressed miRNAs (DEmiRs) and differentially expressed lncRNAs (DELs) data by published literature. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein-protein interaction (PPI), and gene set enrichment analysis (GSEA) analysis were performed. DEmiRs were verified in GSE21346, and the regulatory network of hub mRNAs, DELs, and DEmiRs were constructed. RESULTS. Overall, 40 upregulated and 40 downregulated differentially expressed genes (DEGs) were obtained. The KEGG enrichment showed the DEGs mainly involved in extracellular matrix (ECM)-receptor interaction, focal adhesion, and PI3K-Akt signaling pathway. The GSEA results showed that cornification, keratinization, and cornified envelope were significantly enriched. The validation outcome confirmed six upregulated DEmiRs (miR-766-3p, miR-184, miR-143-3p, miR-138-5p, miR-518b, and miR-1236-3p) and two downregulated DEmiRs (miR-200b-3p and miR-200a-3p). Then, a ceRNA regulatory network was constructed with 22 upregulated and 15 downregulated DEmiRs, 4 downregulated DELs, and 26 upregulated and 33 downregulated DEGs. The network showed that lncRNA SNHG1/miR-766-3p/FOS and some miRNA-mRNA axes were dysregulated in pterygium. CONCLUSIONS. Our study provides a novel perspective on the regulatory mechanism of pterygium, and lncRNA SNHG1/miR-766-3p/FOS may contribute to pterygium development.

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Section: Discussionmentioning

confidence: 59%

Exploring the Molecular Mechanisms of Pterygium by Constructing lncRNA–miRNA–mRNA Regulatory Network

Cui

Dong

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…FN1, an important factor involved in cell adhesion and migration processes, was enriched in the PPI network in this study (Cai et al, 2017). Transforming growth factor-β is a master switch for myofibroblasts, which can induce the synthesis of FN1 and α-SMA in primary human pterygium fibroblasts and primary human conjunctival fibroblasts, and the expression levels of TGF-β2 and TGF-β3 were both upregulated in this study (Di Girolamo et al, 2004;Chen et al, 2019). VIM is a major cytoskeletal component of mesenchymal cells.…”

Section: Discussionmentioning

confidence: 62%

Comparative Transcriptomic Analysis to Identify the Important Coding and Non-coding RNAs Involved in the Pathogenesis of Pterygium

et al. 2021

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Pterygium is a common ocular surface disease characterized by abnormal fibrovascular proliferation and invasion, similar to tumorigenesis. The formation of tumors is related to a change in the expression of various RNAs; however, whether they are involved in the formation and development of pterygium remains unclear. In this study, transcriptome analysis of messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) of paired pterygium and normal conjunctiva was performed to explore key genes regulating the development of pterygium. In total, 579 mRNAs, 275 lncRNAs, and 21 circRNAs were differentially expressed (DE) in pterygium compared with paired conjunctival tissues. Functional enrichment analysis indicated that DE RNAs were associated with extracellular matrix organization, blood vessel morphogenesis, and focal adhesion. Furthermore, through protein-protein interaction network and mRNA-lncRNA co-expression network analysis, key mRNAs including FN1, VCAM1, and MMP2, and key lncRNAs including MIR4435-2HG and LINC00968 were screened and might be involved in the pathogenesis of pterygium. In addition, several circRNAs including hsa_circ_0007482 and hsa_circ_001730 were considered to be involved in the pterygium development. This study provides a scientific basis for elucidating the pathogenesis of pterygium and will be beneficial for the development of preventive and therapeutic strategies.

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“…Moreover, the PI3K/Akt pathway is involved in fibronectin and collagen expression in fibroblasts (35,(40)(41)(42). We focused on PI3K/Akt signaling, which was significantly affected by SAHA, and confirmed that SAHA increased the expression of PTEN.…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 58%

“…ERK activation induces increased actin stress fibers, α-SMA, and fibronectin expression in TM cells (30). ERK inhibition also suppresses TGF-β-induced expression of α-SMA, collagen, and fibronectin in conjunctival, lung, and cardiac fibroblast cells (35)(36)(37).…”

Section: Discussionmentioning

confidence: 97%

Suberoylanilide hydroxamic acid (SAHA) inhibits transforming growth factor-beta 2-induced increases in aqueous humor outflow resistance

Fujimoto

Inoue-Mochita

Iraha

et al. 2021

Journal of Biological Chemistry

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Bromfenac Inhibits TGF-β1–Induced Fibrotic Effects in Human Pterygium and Conjunctival Fibroblasts

Cited by 13 publications

References 49 publications

Exploring the Molecular Mechanisms of Pterygium by Constructing lncRNA–miRNA–mRNA Regulatory Network

Exploring the Molecular Mechanisms of Pterygium by Constructing lncRNA–miRNA–mRNA Regulatory Network

Comparative Transcriptomic Analysis to Identify the Important Coding and Non-coding RNAs Involved in the Pathogenesis of Pterygium

Suberoylanilide hydroxamic acid (SAHA) inhibits transforming growth factor-beta 2-induced increases in aqueous humor outflow resistance

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