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高糖条件下HRCECs中GALNT2与p-EGFR相关性研究
A Study on the Correlation between GALNT2 in HRCECs and p-EGFR under High Sugar Conditions

DOI: 10.12677/acm.2024.1461953, PP. 1593-1602

Keywords: 糖尿病视网膜病变,多肽N-乙酰半乳糖胺转移酶2,p-EGFR抑制剂
Diabetes Retinopathy
, Peptide N-Acetylgalactosamine Transferase 2, P-EGFR Inhibitor

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Abstract:

目的:探讨在高糖条件下敲低多肽N-乙酰半乳糖胺转移酶2 (GALNT2)与抑制磷酸化表皮生长因子受体(Phosphorylated epidermal growth factor receptor, p-EGFR)对视网膜血管内皮细胞(HRCECs)增生及凋亡的影响。方法:本研究以高糖(25 mmol·L1)状态下体外培养的HRCECs为研究对象,将HRCECs分为mock组(25 mmol·L1葡萄糖)、mock + shGALNT2组(25 mmol·L1葡萄糖 + GALNT2敲低病毒)、mock + NC-shGALNT2 + Chrysophanol组(25 mmol·L1葡萄糖 + 对照病毒 + Chrysophanol)、mock + shGALNT2 + Chrysophanol组(25 mmol·L1葡萄糖 + GALNT2敲低病毒 + Chrysophanol),连同培养液在37℃恒温培养箱中培养24 h,比较各组GALNT2 mRNA相对表达量、细胞增生值、细胞凋亡率,以及GALNT2、EGFR、EGF、p-EGFR蛋白相对表达量。结果:mock组、mock + shGALNT2、mock + NC-shGALNT2 + Chrysophanol组和mock + shGALNT2 + Chrysophanol组细胞中GALNT2 mRNA相对表达量比较,差异有统计学意义(P < 0.001)。mock + NC-shGALNT2 + Chrysophanol组和mock + shGALNT2 + Chrysophanol组中细胞增生值低于mock + shGALNT2组,差异具有统计学意义(P < 0.001);mock + shGALNT2 + Chrysophanol组中细胞增生值高于mock + NC-shGALNT2 + Chrysophanol组,差异具有统计学意义(P < 0.001)。mock组、mock + shGALNT2组、mock + NC-shGALNT2 + Chrysophanol组和mock + shGALNT2 + Chrysophanol组细胞凋亡率分别为(8.66 ± 0.22)%、(5.47 ± 0.16)%、(11.94 ± 0.85)%和(6.70 ± 0.26)%,总体比较差异有统计学意义(F = 96.56, P < 0.001)。mock + shGALNT2 + chrysophanol组细胞凋亡率高于mock + shGALNT2组,差异有统计学意义(P < 0.001);mock + shGALNT2 + chrysophanol组细胞凋亡率低于mock + NC-shGALNT2 + chrysophanol组,差异有统计学意义(P < 0.001)。mock + NC-shGALNT2 + Chrysophanol 组和mock + shGALNT2 + Chrysophanol组GALNT2蛋白相对表达量高于mock + shGALNT2组,差异有统计学意义(P < 0.001)。mock + NC-shGALNT2 + Chrysophanol组EGF、EGFR、p-EGFR蛋白相对表达量高于mock + shGALNT2组,但差异无统计学意义(P > 0.05)。结论:在高糖条件下,敲低的GALNT2可以通过介导p-EGFR可以提高HRCECs细胞的增殖能力,减少HRCECs细胞的凋亡。
Objective: To investigate the effects of knocking down peptide N-acetylgalactosamine transferase 2 (GALNT2) and inhibiting phosphorylation of epidermal growth factor receptor under high glucose conditions on the proliferation and apoptosis of retinal vascular endothelial cells (HRCECs). Method: This study focuses on cultured HRCECs in vitro under high glucose (25 mmol·L1) conditions, and divides them into a mock group (25 mmol·L1 glucose), mock + shGALNT2 group (25 mmol·L1 glucose + GALNT2 knockdown virus), mock + NC-shGALNT2 + Chrysophanol group (25 mmol·L1 glucose + control virus + Chrysophanol), mock + shGALNT2 + Chrysophanol group (25 mmol·L1 glucose + GALNT2 knockdown virus + Chrysophanol) and culture medium were cultured in a constant temperature

References

[1]  孔慧, 崔彦. 糖尿病视网膜病变中视网膜内皮细胞功能障碍的研究进展[J]. 眼科新进展, 2022, 42(9): 753-756.
https://doi.org/10.13389/j.cnki.rao.2022.0155
[2]  吕伯昌, 刘蓓, 刘静, 等. 基因沉默解离素-金属蛋白酶17(ADAM17)对高糖环境下人视网膜微血管内皮细胞通透性、增殖、迁移以及蛋白表达的影响[J]. 眼科新进展, 2017, 37(3): 205-209.
[3]  Tan, T. and Wong, T.Y. (2023) Diabetic Retinopathy: Looking forward to 2030. Frontiers in Endocrinology, 13, Article ID: 1077669.
https://doi.org/10.3389/fendo.2022.1077669
[4]  Perais, J., Agarwal, R., Evans, J.R., Loveman, E., Colquitt, J.L., Owens, D., et al. (2023) Prognostic Factors for the Development and Progression of Proliferative Diabetic Retinopathy in People with Diabetic Retinopathy. Cochrane Database of Systematic Reviews, 2, CD013775.
https://doi.org/10.1002/14651858.cd013775.pub2
[5]  Maugeri, G., D’Amico, A.G., Bucolo, C. and D’Agata, V. (2019) Protective Effect of PACAP-38 on Retinal Pigmented Epithelium in an in Vitro and in Vivo Model of Diabetic Retinopathy through EGFR-Dependent Mechanism. Peptides, 119, Article ID: 170108.
https://doi.org/10.1016/j.peptides.2019.170108
[6]  Kobayashi, Y. and Mitsudomi, T. (2016) Not All Epidermal Growth Factor Receptor Mutations in Lung Cancer Are Created Equal: Perspectives for Individualized Treatment Strategy. Cancer Science, 107, 1179-1186.
https://doi.org/10.1111/cas.12996
[7]  Mitsudomi, T. and Yatabe, Y. (2007) Mutations of the Epidermal Growth Factor Receptor Gene and Related Genes as Determinants of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Sensitivity in Lung Cancer. Cancer Science, 98, 1817-1824.
https://doi.org/10.1111/j.1349-7006.2007.00607.x
[8]  Sun, Z., Xue, H., Wei, Y., Wang, C., Yu, R., Wang, C., et al. (2019) Mucin O-Glycosylating Enzyme GALNT2 Facilitates the Malignant Character of Glioma by Activating the EGFR/PI3K/Akt/mTOR Axis. Clinical Science, 133, 1167-1184.
https://doi.org/10.1042/cs20190145
[9]  Xu, C., Liu, G.D., Feng, L., Zhang, C.H. and Wang, F. (2018) Identification of O-Glcnacylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells. Cellular Physiology and Biochemistry, 49, 1389-1402.
https://doi.org/10.1159/000493444
[10]  Marucci, A., di Mauro, L., Menzaghi, C., Prudente, S., Mangiacotti, D., Fini, G., et al. (2013) GALNT2 Expression Is Reduced in Patients with Type 2 Diabetes: Possible Role of Hyperglycemia. PLOS ONE, 8, e70159.
https://doi.org/10.1371/journal.pone.0070159
[11]  李春宇, 格日勒图. GALNT2与P-EGFR在糖尿病模型鼠视网膜中的表达研究[J]. 内蒙古医学杂志, 2022, 54(5): 517-520.
[12]  Tan, A., Li, T., Ruan, L., Yang, J., Luo, Y., Li, L., et al. (2021) Knockdown of Malat1 Alleviates High-Glucose-Induced Angiogenesis through Regulating miR-205-5P/VEGF-A Axis. Experimental Eye Research, 207, Article ID: 108585.
https://doi.org/10.1016/j.exer.2021.108585
[13]  Yan, Z., Wang, C., Meng, Z., Gan, L., Guo, R., Liu, J., et al. (2022) C1q/TNF-Related Protein 3 Prevents Diabetic Retinopathy via AMPK-Dependent Stabilization of Blood-Retinal Barrier Tight Junctions. Cells, 11, Article No. 779.
https://doi.org/10.3390/cells11050779
[14]  Chen, Q., Xi, X., Ma, J., Wang, X., Xia, Y., Wang, X., et al. (2022) The Mechanism by Which Crocetin Regulates the lncRNA NEAT1/miR-125b-5p/SOX7 Molecular Axis to Inhibit High Glucose-Induced Diabetic Retinopathy. Experimental Eye Research, 222, Article ID: 109157.
https://doi.org/10.1016/j.exer.2022.109157
[15]  Xing, X., Wang, H., Niu, T., Jiang, Y., Shi, X. and Liu, K. (2021) RUNX1 Can Mediate the Glucose and O-Glcnac-Driven Proliferation and Migration of Human Retinal Microvascular Endothelial Cells. BMJ Open Diabetes Research & Care, 9, e001898.
https://doi.org/10.1136/bmjdrc-2020-001898
[16]  Yang, Z., Tan, T., Shao, Y., Wong, T.Y. and Li, X. (2022) Classification of Diabetic Retinopathy: Past, Present and Future. Frontiers in Endocrinology, 13, Article ID: 1079217.
https://doi.org/10.3389/fendo.2022.1079217
[17]  陈晓云, 李建桥, 朱晓波, 等. 复方血栓通对人视网膜血管内皮细胞抗氧化损伤的保护作用及其机制[J]. 中华实验眼科杂志, 2011, 29(10): 872-878.
[18]  吴绵绵, 郭芳, 李亚红, 等. α-黑素细胞刺激素作用后高糖高脂下视网膜血管内皮细胞差异表达基因分析[J]. 中华实验眼科杂志, 2019, 37(9): 694-700.
[19]  Huang, H. (2020) Pericyte-Endothelial Interactions in the Retinal Microvasculature. International Journal of Molecular Sciences, 21, Article No. 7413.
https://doi.org/10.3390/ijms21197413
[20]  Sorrentino, F.S., Matteini, S., Bonifazzi, C., Sebastiani, A. and Parmeggiani, F. (2018) Diabetic Retinopathy and Endothelin System: Microangiopathy versus Endothelial Dysfunction. Eye, 32, 1157-1163.
https://doi.org/10.1038/s41433-018-0032-4
[21]  孙天洋, 格日勒图, 张玉凤, 等. 敲低GALNT2基因对高糖培养的人视网膜血管内皮细胞凋亡的抑制作用及其机制[J]. 中华实验眼科杂志, 2023, 41(9): 846-853.
[22]  Camara-Quintana, J.Q., Nitta, R.T. and Li, G. (2012) Pathology: Commonly Monitored Glioblastoma Markers: EFGR, EGFRvIII, PTEN, and MGMT. Neurosurgery Clinics of North America, 23, 237-246.
https://doi.org/10.1016/j.nec.2012.01.011
[23]  Ju, X., Yang, X., Yan, T., Chen, H., Song, Z., Zhang, Z., et al. (2018) EGFR Inhibitor, AG1478, Inhibits Inflammatory Infiltration and Angiogenesis in Mice with Diabetic Retinopathy. Clinical and Experimental Pharmacology and Physiology, 46, 75-85.
https://doi.org/10.1111/1440-1681.13029
[24]  李涛, 杨丽霞, 高博, 等. JAK/STAT信号通路干预糖尿病微血管并发症研究进展[J]. 中国临床药理学与治疗学, 2023, 28(12): 1415-1421.
[25]  Wu, Y., Liu, C., Hu, R., Huang, M., Lee, J., Chen, C., et al. (2011) Mucin Glycosylating Enzyme GALNT2 Regulates the Malignant Character of Hepatocellular Carcinoma by Modifying the EGF Receptor. Cancer Research, 71, 7270-7279.
https://doi.org/10.1158/0008-5472.can-11-1161
[26]  Wang, X., McCullough, K.D., Franke, T.F. and Holbrook, N.J. (2000) Epidermal Growth Factor Receptor-Dependent Akt Activation by Oxidative Stress Enhances Cell Survival. Journal of Biological Chemistry, 275, 14624-14631.
https://doi.org/10.1074/jbc.275.19.14624
[27]  曹航, 邓文慧, 陈刘月, 等. PI3K通路抑制剂在卵巢癌化疗治疗中的研究进展[J]. 牡丹江医学院学报, 2022, 43(5): 124-127.

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