Transthyretin affects the proliferation and migration of human retinal microvascular endothelial cells in hyperglycemia via hnRNPA2B1

Gu, Yuxuan; Hu, Di; Xin, Yu; Shao, Jun

doi:10.1016/j.bbrc.2021.04.035

Cited by 8 publications

(22 citation statements)

References 20 publications

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“…By searching related literature of these six RBPs, we found that HNRNPA2B1, CALR, EIF1, and POLR2A are associated with DR. The TR-hnRNPA2B1 complex has been reported to repress proliferation, migration, and tube formation of HRECs in hyperglycemia through the STAT-4/miR-223-3p/FBXW7 signaling pathway [ 48 ]. Calr expression is altered in the retina of rats with diabetic retinopathy compared to healthy control rats [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

RNA-Binding Proteins and Alternative Splicing Genes Are Coregulated in Human Retinal Endothelial Cells Treated with High Glucose

Zhao

Kong

Wang

et al. 2022

Journal of Diabetes Research

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To explore the relevant RNA-binding proteins (RBPs) and alternative splicing events (ASEs) in diabetic retinopathy (DR). We devised a comprehensive work to integrate analyses of the differentially expressed genes, including differential RBPs, and variable splicing characteristics related to DR in human retinal endothelial cells induced by low glucose and high glucose in dataset GSE117238. A total of 2320 differentially expressed genes (DEGs) were identified, including 1228 upregulated genes and 1092 downregulated genes. Further analysis screened out 232 RBP genes, and 42 AS genes overlapped DEGs. We selected high expression and consistency six RBP genes (FUS, HNRNPA2B1, CANX, EIF1, CALR, and POLR2A) for coexpression analysis. Through analysis, we found eight RASGs (MDM2, GOLGA2P7, NFE2L1, KDM4A, FAM111A, CIRBP, IDH1, and MCM7) that could be regulated by RBP. The coexpression network was conducted to further elucidate the regulatory and interaction relationship between RBPs and AS. Apoptotic progress, protein phosphorylation, and NF-kappaB cascade revealed by the functional enrichment analysis of RASGs regulated by RBPs were closely related to diabetic retinopathy. Furthermore, the expression of differentially expressed RBPs was validated by qRT-PCR in mouse retinal microvascular endothelial cells and retinas from the streptozotocin mouse model. The results showed that Fus, Hnrnpa2b1, Canx, Calr, and Polr2a were remarkedly difference in high-glucose-treated retinal microvascular endothelial cells and Fus, Hnrnpa2b1, Canx, and Calr were remarkedly difference in retinas from streptozotocin-induced diabetic mice compared to control. The regulatory network between identified RBPs and RASGs suggests the presence of several signaling pathways possibly involved in the pathogenesis of DR. The verified RBPs should be further addressed by future studies investigating associations between RBPs and the downstream of AS, as they could serve as potential biomarkers and targets for DR.

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Section: Discussionmentioning

confidence: 99%

RNA-Binding Proteins and Alternative Splicing Genes Are Coregulated in Human Retinal Endothelial Cells Treated with High Glucose

Zhao

Kong

Wang

et al. 2022

Journal of Diabetes Research

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“…As described in our previous work (18)(19)(20), hRECs were inoculated in the Transwell insert, incubated for 30 h, fixed with 4% paraformaldehyde, stained with crystal violet, and counted under light microscope. Using a wound healing assay kit (ab242285), the hRECs were plated in six-well culture dishes and grown to confluence.…”

Section: Cell Migration and Healingmentioning

confidence: 99%

“…After a 0.5 h incubation at 37 ℃ in in a 48-well plate, the hRECs were inoculated into the basement membrane matrix (BD Biosciences) for a further 3 h incubation at 37 ℃, and the tube formation process was observed and monitored using an Olympus IX-73 microscope (18)(19)(20).…”

Section: Tube Formationmentioning

confidence: 99%

“…As described in our previous work (18)(19)(20), after extraction of the total RNAs and total miRNAs, the expression of PTPN12 mRNA and circ_0007411 in hRECs was detected using Moloney murine leukemia virus (M-MLV) reverse transcriptase and a SYBR Green Real-Time PCR Master Mix (Invitrogen, Carlsbad, CA, USA), with GAPDH was as the internal control. The level of miR-548M was detected using the mirVana TM qRT-PCR miRNA detection kit (Invitrogen, Carlsbad, CA, USA), with cel-miR-39-3p spike-in as the internal control.…”

Section: Qrt-pcrmentioning

confidence: 99%

“…In our previous work, transthyretin (TTR) was shown to have an anti-angiogenic function in DR, mediated through the PABPC1/lncRNA MEG3/miR-223-3p/FBXW7 and hnRNPA2B1/STAT4/miR-223-3p/FBXW7 signaling axes (18)(19)(20). However, it is not known if TTR can affect or regulate circRNAs.…”

Section: Introductionmentioning

confidence: 99%

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Transthyretin-induced increase in circ_0007411 represses neovascularization of human retinal microvascular endothelial cells in hyperglycemia via the miR-548m/PTPN12/SKP1/EGFR pathway

Hu¹,

Tian²,

Lu³

et al. 2022

Ann Transl Med

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Background: To investigate the mechanism of transthyretin (TTR) induced high expression of circ_0007411 and its parent gene, protein tyrosine phosphatase nonreceptor type 12 (PTPN12) in human retinal microvascular endothelial cells (hRECs) cultivated under high glucose condition. Methods:The levels of PTPN12, circ_0007411, miR-548m, S-phase kinase associated protein 1 (SKP1) and epidermal growth factor receptor (EGFR) were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The direct interaction between circ_0007411/PTPN12 and miR-548m was investigated via Dual-luciferase reporter assay. The physiological characterization of hRECs was investigated through Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) labelling, Transwell, flow cytometry (FCM), wound healing, and tube formation assays. Co-immunoprecipitation (Co-IP) was used to detect the interaction between PTPN12 and SKP1. The function of PTPN12 against diabetic retinopathy (DR) was studied in streptozotocin (STZ) induced DR C57BL/6 mice.Results: The levels of circ_0007411 was increased in hRECs in hyperglycemia with the induction of TTR.The overexpressed circ_0007411 could significantly enhance the level of PTPN12 and repress that of miR-548m, and it could enhance apoptosis and prohibit the proliferation, migration, and tube formation of hRECs. miR-548m mimics enhanced the proliferation, migration, and tube formation of hRECs by reducing the expression level of PTPN12 and promoting that of EGFR, whereas circ_0007411 rescued it. The direct binding of PTPN12 and SKP1 was confirmed by Co-IP. Additionally, the anti-neovascularization function of PTPN12 was confirmed in a STZ-induced mouse model of DR. Conclusions:In hyperglycemia, the TTR-induced increase in circ_0007411 could repress retinal neovascularization via the miR-548m/PTPN12/SKP1/EGFR pathway.

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Role of mRNA-binding proteins in retinal neovascularization

Lin,

Cao,

Chen

et al. 2024

Experimental Eye Research

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Transthyretin affects the proliferation and migration of human retinal microvascular endothelial cells in hyperglycemia via hnRNPA2B1

Cited by 8 publications

References 20 publications

RNA-Binding Proteins and Alternative Splicing Genes Are Coregulated in Human Retinal Endothelial Cells Treated with High Glucose

RNA-Binding Proteins and Alternative Splicing Genes Are Coregulated in Human Retinal Endothelial Cells Treated with High Glucose

Transthyretin-induced increase in circ_0007411 represses neovascularization of human retinal microvascular endothelial cells in hyperglycemia via the miR-548m/PTPN12/SKP1/EGFR pathway

Role of mRNA-binding proteins in retinal neovascularization

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