Pterygium: new insights

Chu, Wai Kit; Choi, Hiu Lam; Bhat, Amar; Jhanji, Vishal

doi:10.1038/s41433-020-0786-3

Cited by 101 publications

(106 citation statements)

References 30 publications

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“… 34 , 35 EGR1 was found to suppress cell survival, proliferation, and activates expression of p53 and TGF-beta, 36 which was proved to play a pivotal role in the occurrence of pterygium. 8 , 37 , 38 FN1 and COL1A1 were key molecules in EMT, and were demonstrated to be involved in the pathogenic mechanism of pterygium. 28 Further studies were required to elucidate the complex interaction with these genes and clinical features.…”

Section: Discussionmentioning

confidence: 99%

“…Previous clinical and laboratorial studies showed that immunologic mechanisms, extracellular matrix (ECM) modulation under ultraviolet radiation exposure, cell proliferation and hyperplasia, inflammation, angiogenesis, cholesterol metabolism modification, and hereditary factors attributed to the pathogenesis of pterygium. 7 , 8 Moreover, in recent years, the discovery of non-coding RNAs (regulatory RNAs) made the molecular etiology of pterygium more complex.…”

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confidence: 99%

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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: 99%

mentioning

confidence: 99%

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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“…Pterygium is a fibrovascular disease of the ocular surface with dysregulated cell proliferation and differentiation. [53][54][55] The increased levels of BMP6 in pterygium are contradictory to its role in normal CE, reminiscent of TGF-β having contradictory roles in normal and pathological conditions. 70 However, given that BMP6 regulates both proliferation and differentiation and is upregulated in different tumors and fibrotic conjunctival scars, 46 its increased expression in pterygium comes as no surprise.…”

Section: Discussionmentioning

confidence: 99%

“…Pterygium refers to a group of conjunctival fibrovascular degenerations with diverse etiologies that resemble presquamous metaplasia and affect vision by progressively encroaching into the cornea. [53][54][55] Considering that (1) pterygium is associated with suppression of cyclin-dependent kinase inhibitor p21, 56 (2) BMP6 is upregulated in scarred conjunctival tissue 46 and its upregulation is associated with tumor aggressiveness, 57 and (3) the data presented thus far indicate that BMP6 regulates CE cell proliferation and differentiation in a cyclin-and p21-dependent manner, we tested whether or not BMP6 is altered in pterygium. RT-qPCR revealed significant upregulation of BMP6 transcripts coupled with significant downregulation of transcripts encoding cell cycle suppressors KLF4 and p21, as well as Noggin, in pterygium tissues compared with the normal CE (Fig.…”

Section: Elevated Bmp6 Expression Coupled With Downregulation Of Noggmentioning

confidence: 99%

BMP6 Regulates Corneal Epithelial Cell Stratification by Coordinating Their Proliferation and Differentiation and Is Upregulated in Pterygium

Tiwari

Campbell

Jhanji

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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Proper balance between cell proliferation and differentiation is essential for corneal epithelial (CE) stratification and homeostasis. Although bone morphogenetic protein-6 (BMP6) is known to be expressed in the CE for over 25 years, its function in this tissue remains unknown. Here, we test the hypothesis that BMP6 promotes CE cell stratification and homeostasis by regulating their proliferation and differentiation. METHODS. We employed postnatal day-12 (PN-12), PN-14, PN-20, and PN-90 mouse eyes; human corneal limbal epithelial (HCLE) cells; and ocular surface fibrovascular disease pterygium tissues to evaluate the role of BMP6 in CE proliferation, differentiation, and pathology by RT-qPCR, immunoblots, and/or immunofluorescent staining. Cell proliferation was quantified by immunostaining for Ki67. RESULTS. Coincident with the mouse CE stratification between PN-12 and PN-20, BMP6 was significantly upregulated and the BMP6 antagonist Noggin downregulated. Mature CE retained high BMP6 and low Noggin expression at PN-90. BMP6 and its receptors BMPR1A and BMPR2 were upregulated during in vitro stratification of HCLE cells. Consistent with its anti-proliferative role, exogenous BMP6 suppressed HCLE cell proliferation, downregulated cyclin-D1 and cyclin-D2, and upregulated cell-cycle inhibitors Krüppellike factor 4 (KLF4) and p21. BMP6 also upregulated the desmosomal cadherins desmoplakin and desmoglein in HCLE cells, consistent with its pro-differentiation role. Human pterygium displayed significant upregulation of BMP6 coupled with downregulation of Noggin and cell-cycle suppressors KLF4 and p21. CONCLUSIONS. BMP6 coordinates CE stratification and homeostasis by regulating their proliferation and differentiation. BMP6 is significantly upregulated in human pterygium concurrent with downregulation of Noggin, KLF4, and p21.

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“…The combination of active p53 transcription with the absence of the p53 ubiquitin ligase MDM2 seems to account for the abundant presence of p53 in the cytoplasm of the corneal epithelium. Vice versa, recent research indicates high expression of MDM2 in pterygium tissues and hypothesize that enhanced p53 inhibition by MDM2 could play a role in the occurrence of www.nature.com/scientificreports www.nature.com/scientificreports/ pterygium 21,25 . In similar way, we hypothesize that MDM2 absents in corneal epithelium enables high p53 stability, enhance its concentration and leads to local anti-cancer defense.…”

Section: Discussionmentioning

confidence: 99%

Features of p53 protein distribution in the corneal epithelium and corneal tear film

Tendler

Panshin

2020

Sci Rep

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Tumor suppressor protein p53 is the key factor in the regulation of cell proliferation. Its concentration is low in the cytoplasm of most cell types. However, in corneal epithelium cells, abnormally high p53 content is detected. The aim of the present study was to characterize p53 distribution in the corneal epithelium. For this purpose, immunohistochemistry, western blot analysis and electronic microscope examinations were performed. A low level of p53 was identified in the lens, iris and retina; by contrast, a significantly high concentration of this protein was observed in the corneal epithelium. In opposite, MDM2 was identified in the lens, iris and retina while it is completely absent in the corneal epithelium. In addition, we found a significant amount of exosomes and other microvesicles containing p53 in the corneal mucin layer. We thus hypothesize that a significantly high level of p53 was caused by a combination of absents of MDM2 in parallel with p53 microvesicles storage.

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Pterygium: new insights

Cited by 101 publications

References 30 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

BMP6 Regulates Corneal Epithelial Cell Stratification by Coordinating Their Proliferation and Differentiation and Is Upregulated in Pterygium

Features of p53 protein distribution in the corneal epithelium and corneal tear film

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