AREG is involved in scleral remodeling in form‐deprivation myopia via the ERK1/2‐MMP‐2 pathway

She, Man; Li, Tao; Shi, Wen‐Qing; Li, Bing; Zhou, Xiaodong

doi:10.1096/fj.202200132r

Cited by 4 publications

(4 citation statements)

References 41 publications

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“…In mice overexpressing adcy1, the levels of p-ERK in the forebrain are elevated above normal [ 48 ]. Elevated expression of p-ERK aggravates scleral remodeling in myopia [ 49 ]. Because adcy1 activity can be dynamically regulated by calcium and neuronal stimulation, adcy1 function is related to the regulation of neuronal signal transduction [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

“…Scleral remodeling is known to be closely related to myopia development [ 35 , 36 ]. Studies have shown that phosphorylation of ERK1/2 leads to the upregulation of MMP-2 transcription and translation, which then regulates ECM degradation and causes scleral remodeling in FDM guinea pigs [ 49 ]. It was recently reported that ADCY1 activation stimulates ERK phosphorylation [ 48 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

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LncRNA-XR_002792574.1-mediated ceRNA network reveals potential biomarkers in myopia-induced retinal ganglion cell damage

Wang,

Lin,

Liu

et al. 2023

J Transl Med

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Background Long noncoding RNAs (lncRNAs) play a key role in the occurrence and progression of myopia. However, the function of lncRNAs in retinal ganglion cells (RGCs) in the pathogenesis of myopia is still unknown. The aim of our study was to explore the lncRNA-mediated competing endogenous RNA (ceRNA) network in RGCs during the development of myopia. Methods RNA sequencing was performed to analyze lncRNA and mRNA expression profiles in RGCs between guinea pigs with form-deprived myopia (FDM) and normal control guinea pigs, and related ceRNA networks were constructed. Then, potentially important genes in ceRNA networks were verified by qRT‒PCR, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore biological functions in the RGCs of FDM guinea pigs. The important genes and related signaling pathways were further verified by qRT‒PCR, immunohistochemistry, immunofluorescence and Western blot in myopia in FDM guinea pigs, FDM mice, and highly myopic adults. Results The distribution of RGCs was uneven, the number of RGCs was decreased, and RGC apoptosis was increased in FDM guinea pigs. In total, 873 lncRNAs and 2480 mRNAs were determined to be differentially expressed genes in RGCs from normal control and FDM guinea pigs. Via lncRNA-mediated ceRNA network construction and PCR verification, we found that lncRNA-XR_002792574.1 may be involved in the development of myopia through the miR-760-3p/Adcy1 pathway in RGCs. Further verification in FDM guinea pigs, FDM mice, and highly myopic adults demonstrated that the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis in RGCs might be related to cGMP/PKG, the apelin signaling pathway and scleral remodeling. Conclusion We demonstrated that the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis in RGCs might be related to myopia. On the one hand, the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis might inhibit the cGMP/PKG and apelin signaling pathways in RGCs, thereby causing RGC damage in myopia. On the other hand, the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis may cause myopic scleral remodeling through the ERK-MMP-2 pathway. These findings may reveal novel potential targets in myopia and provide reference value for exploration and development of gene editing therapeutics for hereditary myopia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

LncRNA-XR_002792574.1-mediated ceRNA network reveals potential biomarkers in myopia-induced retinal ganglion cell damage

Wang,

Lin,

Liu

et al. 2023

J Transl Med

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“…In the present study, it was observed that the VEGFA content in the tears of highly myopic patients was signi cantly lower than that of patients in the EM group. Although it is still controversial whether the VEGFA content in the tears of myopic patients can accurately re ect the VEGFA levels in intraocular structures, including the retina and choroid, the change in VEGFA levels in the tears in the current study was used to re ect the change in VEGFA expression in the choroid after onset of myopia to some degree 45,46 . To demonstrate that the reduction in choroidal blood ow in patients with high myopia is caused by a decrease in VEGFA expression in the choroid, we replicated the FDM guinea pig model and observed a signi cant decrease in VEGFA expression in the choroid of myopic guinea pigs, and choroidal atmounts also showed a signi cant decrease in the number of choroidal vessels.…”

Section: Discussionmentioning

confidence: 99%

VEGFA may be a potential marker of myopic choroidal thickness and vascular density changes

Wan

Shi

Liang

et al. 2022

Preprint

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Introduction: To evaluate the changes of choroidal thickness（CT） and blood flow related to myopia, and its effects of vascular endothelial growth factor (VEGFA) on choroidal vessels in myopia. Methods: 137 subjects were included and divided into emmetropia (EM), non-high myopia (Non-HM) and high myopia (HM) groups. we measured choroidal thickness (CT), choriocapillaris vessel density (VD), and VEGFA content in tears in humans and detected the role of VEGFA in the choroid in form-deprivation myopia (FDM) in guinea pigs. Twenty-four guinea pigs were divided into control and Form deprivation myopia (FDM) groups, and the expression changes of choroidal vessels and VEGFA were observed and compared using immunohistochemistry and Western blotting. Twenty-one guinea pigs were divided into control, FDM+Vehicle and FDM+Conbercept groups. The changes of diopter, axis length and choroidal vessels after intravitreal injection of Conbercept were observed. Results: There were significant differences in CT and VD among the three groups (p<0.05). The expression of VEGFA in tears of myopic group decreased significantly, presenting EM< Non-HM <HM group. Compared with the control group, the area fraction of choroidal vessels in the FDM group decreased. we observed a reduction in choroidal vasculature in FDM guinea pigs along with significant downregulation of choroidal VEGFA expression. After intravitreal injection of Conbercept into FDM guinea pigs, the FDM + conbercept group had a greater degree of myopia, longer axial length and less vascular density in the choroid than the control group. Conclusions: we found thinner CT, less choriocapillaris VD, and lower VEGFA content in tears in the myopic group than in the emmetropia group in humans. After intravitreal injection of Conbercept, FDM + conbercept group had a greater degree of myopia, longer axial length and less vascular density in the choroid than the control group. VEGFA may participate in the regulation of choroidal blood vessels and blood flow in myopia. VEGFA may be a potential target for controlling myopia.

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“…According to the literature, we found that Amphiregulin (AREG) is a direct target gene of TAZ (Han, et al 2014;Martini, et al 2017). AREG has been reported to be involved in various physiopathological processes such as cancer (Steponaitis, et al 2019), scleral remodeling (She, et al 2022), skin brosis (Zhang, et al 2021a), bone formation (Raimondo, et al 2019). In cancer, AREG has been validated as an oncogene (Ahn, et al 2013).…”

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confidence: 99%

Partition defective 3 promotes TAZ nuclear localization and promotes Amphiregulin transcription to promote liver hepatocellular carcinoma cell invasion, migration and epithelial mesenchymal

Wang

et al. 2022

Preprint

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Background Partition defective 3 (PARD3) regulates cell polarity and functions as a cancer promoting or tumor suppressor in different cancer types. PARD3 was reported to be highly expressed in liver hepatocellular carcinoma (LIHC) tissues and high expression of PARD3 was significantly associated with poor clinicopathological features and lower overall survival, but whether PARD3 regulated invasion, migration and epithelial mesenchymal transition (EMT) in LIHC has not been reported. Objectives To investigate the effect and mechanism of PARD3 on LIHC cell invasion, migration and EMT. Methods PARD3 expression in LIHC tumor group and relationship with survival were queried according to the GEPIA website. PARD3 mRNA and protein expression in 41 clinical samples were determined by RT-qPCR and immunohistochemistry (IHC), respectively. PARD3, transcriptional coactivator with PDZ-binding motif (TAZ)and amphiregulin ༈AREG༉expression in HepG2 cells with overexpression or knockdown, and the expression of PARD3, TAZ, AREG and EMT related proteins were determined by Western blot. Transwell assay for HepG2cell invasion ability. The migration ability of HepG2 cells was detected by wound healing experiments. TAZ localization was detected by immunofluorescence. Co-IP detected the effect of PARD3 on TAZ and TAZ TEAD binding. The effect of TAZ on AREG transcript levels was examined by RT-qPCR. Results PARD3 was found to be highly expressed in LIHC tumor group by GEPIA website query, and the expression of PARD3 gradually increased with increasing tumor stage, and high expression of PARD3 usually means low overall survival in LIHC. We also found that PARD3 was highly expressed in LIHC tissues. Knockdown of PARD3 inhibited HepG2 cell invasion, migration and EMT, while overexpression of PARD3 played the opposite role. Moreover, PARD3 promotes AREG transcription by promoting TAZ nuclear localization, which in turn promotes LIHC cell invasion, migration and EMT. Conclusion PARD3 promotes TAZ nuclear localization and promotes AREG transcription to promote epithelial mesenchymal transition in LIHC.

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AREG is involved in scleral remodeling in form‐deprivation myopia via the ERK1/2‐MMP‐2 pathway

Cited by 4 publications

References 41 publications

LncRNA-XR_002792574.1-mediated ceRNA network reveals potential biomarkers in myopia-induced retinal ganglion cell damage

LncRNA-XR_002792574.1-mediated ceRNA network reveals potential biomarkers in myopia-induced retinal ganglion cell damage

VEGFA may be a potential marker of myopic choroidal thickness and vascular density changes

Partition defective 3 promotes TAZ nuclear localization and promotes Amphiregulin transcription to promote liver hepatocellular carcinoma cell invasion, migration and epithelial mesenchymal

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