LncRNA TDRG1-Mediated Overexpression of VEGF Aggravated Retinal Microvascular Endothelial Cell Dysfunction in Diabetic Retinopathy

Gong, Qiang; Dong, Wenpei; Fan, Ying; Chen, Feng’e; Bian, Xiaolan; Xu, Xun; Qian, Tianwei; Yu, Ping

doi:10.3389/fphar.2019.01703

Cited by 21 publications

(16 citation statements)

References 38 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…LncRNAs are emerging as critical regulators that impact a variety biological functions and the pathogenesis of diseases 29,30 . Many studies have confirmed that lncRNAs are associated with the proliferation, migration and angiogenesis of HRECs 31,32 , and the abnormal expression of lncRNAs has been observed to be correlated with pathogenesis and progression of DR 33,34 . For example, lncRNA HOXA transcript at the distal tip improves diabetic retinal microangiopathy through the p38 mitogen‐activated protein kinase pathway 35 .…”

Section: Discussionmentioning

confidence: 99%

Long non‐coding ribonucleic acid urothelial carcinoma‐associated 1 promotes high glucose‐induced human retinal endothelial cells angiogenesis through regulating micro‐ribonucleic acid‐624‐3p/vascular endothelial growth factor C

Huang

Yao

et al. 2021

J of Diabetes Invest

View full text Add to dashboard Cite

Aims/Introduction Emerging evidence has indicated that long non‐coding ribonucleic acids play important roles in the development and progression of diabetic retinopathy (DR). It is reported that urothelial carcinoma‐associated 1 (UCA1) is highly expressed in diabetic lymphoendothelial cells and influences glucose metabolism in rats with DR. The aim of the present study was to explore the role of UCA1 in the mechanism of DR. Materials and Methods Gene expression analyses in fibrovascular membranes excised from patients with DR using public microarray datasets (GSE60436). Reverse transcription polymerase chain reaction was carried out to detect UCA1, micro‐ribonucleic acid (miR)‐624‐3p and vascular endothelial growth factor C (VEGF‐C) expressions in the blood of patients and human retinal endothelial cells (HRECs). Furthermore, Cell Counting kit‐8, Transwell assay, and tube formation assay were used to identify biological effects of UCA1 on HRECs proliferation, migration ability and angiogenesis in vitro. Results UCA1 and VEGF‐C were elevated in DR patients and high glucose‐induced HRECs cell lines, whereas miR‐624‐3p was decreased. UCA1 inhibition inhibited proliferation, angiogenesis and migration of HRECs cells under high‐glucose condition. Luciferase reporter assay showed that UCA1 could sponge with miR‐624‐3p, which could directly target VEGF‐C. Finally, we proved a pathway that UCA1 promoted cell proliferation, migration and angiogenesis through sponging with miR‐624‐3p, thereby upregulating VEGF‐C in high‐glucose‐induced HRECs. Conclusions We identified UCA1 as an important factor associated with DR, which could regulate the expression of VEGF‐C by sponging miR‐624‐3p in human retinal endothelial cells. Our results pave the way for further studies on diagnostic and therapeutic studies related to UCA1 in DR patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Long non‐coding ribonucleic acid urothelial carcinoma‐associated 1 promotes high glucose‐induced human retinal endothelial cells angiogenesis through regulating micro‐ribonucleic acid‐624‐3p/vascular endothelial growth factor C

Huang

Yao

et al. 2021

J of Diabetes Invest

View full text Add to dashboard Cite

show abstract

“…For example, lncRNA-MIAT can regulate microvascular dysfunction by functioning as a ceRNA [ 25 ]. In addition, Gong et al suggested that LncRNA TDRG1 aggravates retinal microvascular endothelial cell dysfunction in diabetic retinopathy through upregulating VEGF [ 26 ]. With the development of high-throughput sequencing, a large number of novel lncRNA were identified in DV.…”

Section: Discussionmentioning

confidence: 99%

Construction of lncRNA-related ceRNA regulatory network in diabetic subdermal endothelial cells

Wan

Liu

2021

Bioengineered

View full text Add to dashboard Cite

Long non-coding RNAs (lncRNAs) were considered to be involved in vascular complications in diabetes mellitus, but still only limited knowledge in this regard has been obtained. Herein, we further explored the roles of lncRNAs and mRNAs in diabetic vasculopathy (DV) through conducting bioinformatics analysis using data set downloaded from GEO database. The differentially expressed lncRNAs and mRNAs were identified by edge package. GO enrichment analysis and KEGG pathway analysis were performed based on clusterprofiler package. The relationship between lncRNA and miRNA was predicted using starBase database, and the potential mRNAs targeted by miRNAs were predicted by TargetScan, miRTarbase and miRDB database. The string database was used to analyze the protein-protein interaction (PPI). As a result, a total of 12 lncRNAs and 711 mRNAs were found to be differentially expressed in the diabetic subdermal endothelial cells compared with normal controls. A ceRNA network was established, which was composed of seven lncRNA nodes, 49 miRNA nodes, 58 mRNA nodes and 183 edges, and MSC-AS1 and LINC01550 may serve as key nodes. GO function enrichment analysis showed enrichments of epithelial cell proliferation, intercellular junction, and cell adhesion molecule binding. KEGG pathway analysis revealed 33 enriched pathways. PPI protein interaction analysis identified 57 potential ceRNA-related proteins. Overall, this study suggests that multiple lncRNAs, specifically MSC-AS1 and LINC01550, may play an important role in DV development and they are like to be developed as the therapeutic targets for DV. However, further experiments in vitro and in vivo should be conducted to validate our results.

show abstract

“…Other lncRNAs functioning during retinal development are summarized in Table 2 . Interestingly aberrant expression of lncRNAs has been associated with visual impairments such as diabetic retinopathy (Malat1, Miat, Tdrg1, Hottip, circHIPK3) [ 138 – 141 ], retinoblastoma (Bancr, Meg3) and glaucoma (CDKN2B-As1) [ 124 , 141 ]. Mechanistically, data generated thus far suggest that most of these lncRNAs guide chromatin modifiers, mostly PRC2 and H3K9 methyltransferases, to specific genomic loci to modulate gene expression [ 127 , 142 – 144 ].…”

Section: Long Non-coding Rna In the Developing Retinamentioning

confidence: 99%

Epigenetic regulation of retinal development

Raeisossadati

Ferrari

Kihara

et al. 2021

Epigenetics & Chromatin

View full text Add to dashboard Cite

In the developing vertebrate retina, retinal progenitor cells (RPCs) proliferate and give rise to terminally differentiated neurons with exquisite spatio-temporal precision. Lineage commitment, fate determination and terminal differentiation are controlled by intricate crosstalk between the genome and epigenome. Indeed, epigenetic regulation plays pivotal roles in numerous cell fate specification and differentiation events in the retina. Moreover, aberrant chromatin structure can contribute to developmental disorders and retinal pathologies. In this review, we highlight recent advances in our understanding of epigenetic regulation in the retina. We also provide insight into several aspects of epigenetic-related regulation that should be investigated in future studies of retinal development and disease. Importantly, focusing on these mechanisms could contribute to the development of novel treatment strategies targeting a variety of retinal disorders.

show abstract

LncRNA TDRG1-Mediated Overexpression of VEGF Aggravated Retinal Microvascular Endothelial Cell Dysfunction in Diabetic Retinopathy

Abstract: Conclusions: LncRNA TDRG1 promoted microvascular cell dysfunction via upregulating VEGF in the progression of DR and may serve as a potential therapeutic target in DR treatment.

Cited by 21 publications

References 38 publications

Long non‐coding ribonucleic acid urothelial carcinoma‐associated 1 promotes high glucose‐induced human retinal endothelial cells angiogenesis through regulating micro‐ribonucleic acid‐624‐3p/vascular endothelial growth factor C

Long non‐coding ribonucleic acid urothelial carcinoma‐associated 1 promotes high glucose‐induced human retinal endothelial cells angiogenesis through regulating micro‐ribonucleic acid‐624‐3p/vascular endothelial growth factor C

Construction of lncRNA-related ceRNA regulatory network in diabetic subdermal endothelial cells

Epigenetic regulation of retinal development

Contact Info

Product

Resources

About