开放期刊系统

microRNAs 在糖尿病视网膜病变新生血管形成的相关研究进展

文 敏, 陈 晓梅, 范 嗣富, 谢 金凤, 吴 蓉, 黄 胜*

摘要

增殖性糖尿病视网膜病变 (PDR) 的特征是视网膜新生血管形成和视神经纤维损伤,最终导致视力丧失,其发病
机制仍不完全清楚。近年研究发现 microRNAs(miRNAs) 作为糖尿病视网膜病变 VEGF 表达的关键因子,miRNAs 通过
VEGF/JAK2/STAT3 信号通路在糖尿病视网膜新生血管形成中起调控作用。miRNA 已被提出作为 DR 筛查的生物标志物,
同时 miRNA 有可能成为新的 DR 治疗方法。本文综述 miRNA 及其通过 JAK2/STAT3 信号通路在 DR 新生血管形成的作用,
为临床提供一种新的防治策略。

关键词

糖尿病视网膜病变 (DR);microRNAs;(miRNAs);新生血管;JAK2/STAT3 信号通路

全文:

PDF

参考

[1] T. Xu, B. Wang, H. Liu, H. Wang, P. Yin, W. Dong, J.

Li, Y.X. Wang, M. Yusufu, P. Briant, N. Reinig, C. Ashbaugh, J.

Adelson, T. Vos, R. Bourne, N. Wang, and M. Zhou, Prevalence

and causes of vision loss in China from 1990 to 2019: findings

from the Global Burden of Disease Study 2019. Lancet Public

Health 5 (2020) e682-e691.

[2] 雒文娟 , 于麦霞 , 董文萍 . 糖尿病性视网膜病变发病

相关非编码 RNAs 的研究进展 [J/OL]. 医学信息 ,1-6[2024-

08-28].

[3] S.D. Solomon, E. Chew, E.J. Duh, L. Sobrin, J.K. Sun,

B.L. VanderBeek, C.C. Wykoff, and T.W. Gardner, Diabetic

Retinopathy: A Position Statement by the American Diabetes

Association. Diabetes Care 40 (2017) 412-418.

[4] T.Y. Wong, J. Sun, R. Kawasaki, P. Ruamviboonsuk,

N. Gupta, V.C. Lansingh, M. Maia, W. Mathenge, S. Moreker,

M.M.K. Muqit, S. Resnikoff, J. Verdaguer, P. Zhao, F. Ferris, L.P.

Aiello, and H.R. Taylor, Guidelines on Diabetic Eye Care: The

International Council of Ophthalmology Recommendations for

Screening, Follow-up, Referral, and Treatment Based on Resource

Settings. Ophthalmology 125 (2018) 1608-1622.

[5] J. Lechner, O.E. O’Leary, and A.W. Stitt, The pathology

associated with diabetic retinopathy. Vision Res 139 (2017) 7-14.

[6] Q. Kang, and C. Yang, Oxidative stress and diabetic

retinopathy: Molecular mechanisms, pathogenetic role and

therapeutic implications. Redox Biol 37 (2020) 101799.

[7] A.N. Kollias, and M.W. Ulbig, Diabetic retinopathy: Early

diagnosis and effective treatment. Dtsch Arztebl Int 107 (2010)

75-83; quiz 84.

[8] S. Chaudhary, J. Zaveri, and N. Becker, Proliferative

diabetic retinopathy (PDR). Dis Mon 67 (2021) 101140.

[9] 李 宝 花 , 亢 泽 峰 , 侯 昕 玥 , 等 .PI3K/AKT 通 路

在 糖 尿 病 视 网 膜 病 变 中 的 调 控 作 用 [J]. 国 际 眼 科 杂

志 ,2024,24(09):1426-1431.

[10] Y. He, Y. Dan, X. Gao, L. Huang, H. Lv, and J. Chen,

DNMT1-mediated lncRNA MEG3 methylation accelerates

endothelial-mesenchymal transition in diabetic retinopathy

through the PI3K/Akt/mTOR signaling pathway. Am J Physiol

Endocrinol Metab 320 (2021) E598-e608.

[11] A.J. Duraisamy, M. Mishra, A. Kowluru, and R.A.

Kowluru, Epigenetics and Regulation of Oxidative Stress in

Diabetic Retinopathy. Invest Ophthalmol Vis Sci 59 (2018) 4831-

4840.

[12] K. Becker, H. Klein, E. Simon, C. Viollet, C. Haslinger,

G. Leparc, C. Schultheis, V. Chong, M.H. Kuehn, F. FernandezAlbert, and R.A. Bakker, In-depth transcriptomic analysis of

human retina reveals molecular mechanisms underlying diabetic

retinopathy. Sci Rep 11 (2021) 10494.

[13] X. Li, Z.W. Yu, Y. Wang, Y.H. Fu, and X.Y. Gao,

MicroRNAs: Potential Targets in Diabetic Retinopathy. Horm

Metab Res 52 (2020) 142-148.

[14] F. Gui, Z. You, S. Fu, H. Wu, and Y. Zhang, Endothelial

Dysfunction in Diabetic Retinopathy. Front Endocrinol (Lausanne)

11 (2020) 591.

[15] X. Zhao, F. Ling, G.W. Zhang, N. Yu, J. Yang, and

X.Y. Xin, The Correlation Between MicroRNAs and Diabetic

Retinopathy. Front Immunol 13 (2022) 941982.

[16] A. Milluzzo, A. Maugeri, M. Barchitta, L. Sciacca, and A.

Agodi, Epigenetic Mechanisms in Type 2 Diabetes Retinopathy: A

Systematic Review. Int J Mol Sci 22 (2021).

[17] C.H. Liu, S. Huang, W.R. Britton, and J. Chen,

MicroRNAs in Vascular Eye Diseases. Int J Mol Sci 21 (2020).

[18] D. Shao, S. He, Z. Ye, X. Zhu, W. Sun, W. Fu, T. Ma,

and Z. Li, Identification of potential molecular targets associated

with proliferative diabetic retinopathy. BMC Ophthalmol 20 (2020)

143.

[19] Q. Gong, J. Xie, Y. Liu, Y. Li, and G. Su, Differentially

Expressed MicroRNAs in the Development of Early Diabetic

Retinopathy. J Diabetes Res 2017 (2017) 4727942.

[20] M.U. Kaikkonen, P. Halonen, O.H. Liu, T.A. Turunen,

J. Pajula, P. Moreau, I. Selvarajan, T. Tuomainen, E. Aavik, P.

Tavi, and S. Yl-Herttuala, Genome-Wide Dynamics of Nascent

Noncoding RNA Transcription in Porcine Heart After Myocardial

Infarction. Circ Cardiovasc Genet 10 (2017).

[21] A.R. Gomaa, E.T. Elsayed, and R.F. Moftah,

MicroRNA-200b Expression in the Vitreous Humor of Patients

with Proliferative Diabetic Retinopathy. Ophthalmic Res 58 (2017)

168-175.

[22] R. Haque, E.H. Hur, A.N. Farrell, P.M. Iuvone, and J.C.

Howell, MicroRNA-152 represses VEGF and TGFβ1 expressions

through post-transcriptional inhibition of (Pro)renin receptor in

human retinal endothelial cells. Mol Vis 21 (2015) 224-35.

[23] C.B.M. Platania, R. Maisto, M.C. Trotta, M. D’Amico,

S. Rossi, C. Gesualdo, G. D’Amico, C. Balta, H. Herman, A.

Hermenean, F. Ferraraccio, I. Panarese, F. Drago, and C. Bucolo,

Retinal and circulating miRNA expression patterns in diabetic

retinopathy: An in silico and in vivo approach. Br J Pharmacol 176

(2019) 2179-2194.

[24] F. Huang, J. Bai, J. Zhang, D. Yang, H. Fan, L. Huang,

T. Shi, and G. Lu, Identification of potential diagnostic biomarkers

for pneumonia caused by adenovirus infection in children by

screening serum exosomal microRNAs. Mol Med Rep 19 (2019)

4306-4314.

[25] A. Raghunath, and E. Perumal, Micro-RNAs and their

roles in eye disorders. Ophthalmic Res 53 (2015) 169-86.

[26] P. Kantharidis, B. Wang, R.M. Carew, and H.Y. Lan,

Diabetes complications: the microRNA perspective. Diabetes 60

(2011) 1832-7.

[27] J. Friedrich, D.H.W. Steel, R.O. Schlingemann, M.J.

Koss, H.P. Hammes, G. Krenning, and I. Klaassen, microRNA

Expression Profile in the Vitreous of Proliferative Diabetic

Retinopathy Patients and Differences from Patients Treated with

Anti-VEGF Therapy. Transl Vis Sci Technol 9 (2020) 16.

[28] D. Ye, T. Zhang, G. Lou, W. Xu, F. Dong, G. Chen, and

Y. Liu, Plasma miR-17, miR-20a, miR-20b and miR-122 as

potential biomarkers for diagnosis of NAFLD in type 2 diabetes

mellitus patients. Life Sci 208 (2018) 201-207.

[29] C. Yin, X. Lin, Y. Sun, and X. Ji, Dysregulation of

miR-210 is involved in the development of diabetic retinopathy

and serves a regulatory role in retinal vascular endothelial cell

proliferation. Eur J Med Res 25 (2020) 20.

[30] Z. Smit-McBride, A.T. Nguyen, A.K. Yu, S.P.

Modjtahedi, A.A. Hunter, S. Rashid, E. Moisseiev, and L.S. Morse,

Unique molecular signatures of microRNAs in ocular fluids and

plasma in diabetic retinopathy. PLoS One 15 (2020) e0235541.

[31] C. Wang, Y. Lin, Y. Fu, D. Zhang, and Y. Xin, MiR-

221-3p regulates the microvascular dysfunction in diabetic

retinopathy by targeting TIMP3. Pflugers Arch 472 (2020) 1607-

1618.

[32] L. Zhao, and Q. Pan, Highly-Expressed MiR-221-

3p Distinctly Increases the Incidence of Diabetic Retinopathy in

Patients With Type 2 Diabetes Mellitus. Transl Vis Sci Technol 12

(2023) 17.

[33] L. Li, and S. Li, miR-205-5p inhibits cell migration and

invasion in prostatic carcinoma by targeting ZEB1. Oncol Lett 16

(2018) 1715-1721.

[34] T. Takeno, T. Hasegawa, H. Hasegawa, Y. Ueno, R.

Hamataka, A. Nakajima, J. Okubo, K. Sato, and T. Sakamaki,

MicroRNA-205-5p inhibits three-dimensional spheroid

proliferation of ErbB2-overexpressing breast epithelial cells

through direct targeting of CLCN3. PeerJ 7 (2019) e7799.

[35] Q. Chen, X. Huang, and R. Li, lncRNA MALAT1/miR-

205-5p axis regulates MPP(+)-induced cell apoptosis in MN9D

cells by directly targeting LRRK2. Am J Transl Res 10 (2018)

563-572.

[36] M. Oltra, L. Vidal-Gil, R. Maisto, J. Sancho-Pelluz, and

J.M. Barcia, Oxidative stress-induced angiogenesis is mediated by

miR-205-5p. J Cell Mol Med 24 (2020) 1428-1436.

[37] A. Tan, T. Li, L. Ruan, J. Yang, Y. Luo, L. Li, and X.

Wu, Knockdown of Malat1 alleviates high-glucose-induced

angiogenesis through regulating miR-205-5p/VEGF-A axis. Exp

Eye Res 207 (2021) 108585.

[38] Y.O. Nunez Lopez, G. Garufi, and A.A. Seyhan, Altered

levels of circulating cytokines and microRNAs in lean and obese

individuals with prediabetes and type 2 diabetes. Mol Biosyst 13

(2016) 106-121.

[39] T.S. Assmann, M. Recamonde-Mendoza, B.M. De Souza,

and D. Crispim, MicroRNA expression profiles and type 1 diabetes

mellitus: systematic review and bioinformatic analysis. Endocr

Connect 6 (2017) 773-790.

[40] S. Estrella, D.F. Garcia-Diaz, E. Codner, P. CamachoGuillén, and F. Pérez-Bravo, [Expression of miR-22 and

miR-150 in type 1 diabetes mellitus: Possible relationship with

autoimmunity and clinical characteristics]. Med Clin (Barc) 147

(2016) 245-7.

[41] N. Pescador, M. Pérez-Barba, J.M. Ibarra, A.

Corbatón, M.T. Martínez-Larrad, and M. Serrano-Ríos,

Serum circulating microRNA profiling for identification of

potential type 2 diabetes and obesity biomarkers. PLoS One 8

(2013) e77251.

[42] B. Kovacs, S. Lumayag, C. Cowan, and S. Xu,

MicroRNAs in early diabetic retinopathy in streptozotocininduced diabetic rats. Invest Ophthalmol Vis Sci 52 (2011) 4402-

9.

[43] Y. Duan, B. Zhou, H. Su, Y. Liu, and C. Du, miR-150

regulates high glucose-induced cardiomyocyte hypertrophy by

targeting the transcriptional co-activator p300. Exp Cell Res 319

(2013) 173-84.

[44] L. Shi, A.J. Kim, R.C. Chang, J.Y. Chang, W. Ying,

M.L. Ko, B. Zhou, and G.Y. Ko, Deletion of miR-150 Exacerbates

Retinal Vascular Overgrowth in High-Fat-Diet Induced Diabetic

Mice. PLoS One 11 (2016) e0157543.

[45] F. Yu, S. Chapman, D.L. Pham, M.L. Ko, B. Zhou,

and G.Y. Ko, Decreased miR-150 in obesity-associated type 2

diabetic mice increases intraocular inflammation and exacerbates

retinal dysfunction. BMJ Open Diabetes Res Care 8 (2020).

[46] J.M. Lu, Z.Z. Zhang, X. Ma, S.F. Fang, and X.H. Qin,

Repression of microRNA-21 inhibits retinal vascular endothelial

cell growth and angiogenesis via PTEN dependent-PI3K/Akt/

VEGF signaling pathway in diabetic retinopathy. Exp Eye Res 190

(2020) 107886.

[47] Y.H. Chen, S. Heneidi, J.M. Lee, L.C. Layman, D.W.

Stepp, G.M. Gamboa, B.S. Chen, G. Chazenbalk, and R. Azziz,

miRNA-93 inhibits GLUT4 and is overexpressed in adipose tissue

of polycystic ovary syndrome patients and women with insulin

resistance. Diabetes 62 (2013) 2278-86.

[48] K. Hirota, H. Keino, M. Inoue, H. Ishida, and A.

Hirakata, Comparisons of microRNA expression profiles in

vitreous humor between eyes with macular hole and eyes with

proliferative diabetic retinopathy. Graefes Arch Clin Exp

Ophthalmol 253 (2015) 335-42.

[49] J. Long, Y. Wang, W. Wang, B.H. Chang, and F.R.

Danesh, Identification of microRNA-93 as a novel regulator of

vascular endothelial growth factor in hyperglycemic conditions. J

Biol Chem 285 (2010) 23457-65.

[50] H.L. Zou, Y. Wang, Q. Gang, Y. Zhang, and Y. Sun,

Plasma level of miR-93 is associated with higher risk to develop

type 2 diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol

255 (2017) 1159-1166.

[51] Y. Zhou, S. Abraham, P. Andre, L.C. Edelstein, C.A.

Shaw, C.A. Dangelmaier, A.Y. Tsygankov, S.P. Kunapuli, P.F.

Bray, and S.E. McKenzie, Anti-miR-148a regulates platelet

FcγRIIA signaling and decreases thrombosis in vivo in mice.

Blood 126 (2015) 2871-81.

[52] J.Z. Lacerda, L.C. Ferreira, B.C. Lopes, A.F.

Aristizábal-Pachón, M.C. Bajgelman, T.F. Borin, and D.

Zuccari, Therapeutic Potential of Melatonin in the Regulation of

MiR-148a-3p and Angiogenic Factors in Breast Cancer. Microrna

8 (2019) 237-247.

[53] Z. Liang, K.P. Gao, Y.X. Wang, Z.C. Liu, L. Tian, X.Z.

Yang, J.Y. Ding, W.T. Wu, W.H. Yang, Y.L. Li, Z.B. Zhang, and

R.H. Zhai, RNA sequencing identified specific circulating miRNA

biomarkers for early detection of diabetes retinopathy. Am J

Physiol Endocrinol Metab 315 (2018) E374-e385.

[54] J. Wang, Y. Yao, K. Wang, J. Li, T. Chu, and H. Shen,

MicroRNA-148a-3p alleviates high glucose-induced diabetic

retinopathy by targeting TGFB2 and FGF2. Acta Diabetol 57

(2020) 1435-1443.

[55] M. Jiang, H. Wang, M. Jin, X. Yang, H. Ji, Y. Jiang, H.

Zhang, F. Wu, G. Wu, X. Lai, L. Cai, R. Hu, L. Xu, and L. Li,

Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic

Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting

M2 Microglial/Macrophage Polarization. Cell Physiol Biochem 47

(2018) 864-878.

[56] F. Zhao, Y. Qu, J. Zhu, L. Zhang, L. Huang, H. Liu, S. Li,

and D. Mu, miR-30d-5p Plays an Important Role in Autophagy

and Apoptosis in Developing Rat Brains After Hypoxic-Ischemic

Injury. J Neuropathol Exp Neurol 76 (2017) 709-719.

[57] S. Josson, M. Gururajan, P. Hu, C. Shao, G.Y. Chu, H.E.

Zhau, C. Liu, K. Lao, C.L. Lu, Y.T. Lu, J. Lichterman, S. Nandana,

Q. Li, A. Rogatko, D. Berel, E.M. Posadas, L. Fazli, D. Sareen,

and L.W. Chung, miR-409-3p/-5p promotes tumorigenesis,

epithelial-to-mesenchymal transition, and bone metastasis of

human prostate cancer. Clin Cancer Res 20 (2014) 4636-46.

[58] J.D. Massaro, C.D. Polli, C.E.S. Matheus, C.C. Alves,

G.A. Passos, E.T. Sakamoto-Hojo, R.D.H.M. Wallace, N.J. Bispo

Cezar, D.M. Rassi, and F. Crispim, Post-transcriptional markers

associated with clinical complications in Type 1 and Type 2

diabetes mellitus. Molecular and Cellular Endocrinology (2019).

[59] J.M.W. Walz, ThomasZhang, Pei PeiCakir,

BertanGruening, BjoernAgostini, HansjuergenReuer,

TristanLudwig, FranziskaBoneva, StefaniyaFaerber, LotharLange,

ClemensSchlunck, Guenther R.Stahl, Andreas, Impact of

angiogenic activation and inhibition on miRNA profiles of human

retinal endothelial cells. Experimental Eye Research 181 (2019).

[60] Y. Wang, W. Lin, and J. Ju, MicroRNA-409-5p

promotes retinal neovascularization in diabetic retinopathy. Cell

Cycle 19 (2020) 1314-1325.

[61] A. Smyth, B. Callaghan, C.E. Willoughby, and C.

O’Brien, The Role of miR-29 Family in TGF-β Driven Fibrosis

in Glaucomatous Optic Neuropathy. Int J Mol Sci 23 (2022).

[62] R. Gong, R. Han, X. Zhuang, W. Tang, G. Xu, L. Zhang,

J. Wu, and J. Ma, MiR-375 mitigates retinal angiogenesis by

depressing the JAK2/STAT3 pathway. Aging (Albany NY) 14

(2022) 6594-6604.

[63] M. Ragusa, R. Caltabiano, A. Russo, L. Puzzo, T.

Avitabile, A. Longo, M.D. Toro, C. Di Pietro, M. Purrello, and M.

Reibaldi, MicroRNAs in vitreus humor from patients with ocular

diseases. Mol Vis 19 (2013) 430-40.

[64] 郑方静 , 赖红华 , 赖晓兰 , 等 . 微小 RNA-216a 调控

JAK2/STAT3 通路对鼻咽癌细胞增殖、侵袭、自噬及血管生

成的影响 [J]. 肿瘤学杂志 ,2021,27(11):905-914.

[65] X. Zhan, Y. Wang, and J. Yang, Janus Kinase/Signal

Converters, and the Transcriptional Activator Signaling Pathway

Promotes Lung Cancer Through Increasing M2 Macrophage.

Journal of Biomaterials and Tissue Engineering (2021).

[66] G. Xie, Y. Song, N. Li, Z. Zhang, X. Wang, Y. Liu, S.

Jiao, M. Wei, B. Yu, Y. Wang, H. Wang, and A. Qu, Myeloid

peroxisome proliferator-activated receptor α deficiency

accelerates liver regeneration via IL-6/STAT3 pathway after 2/3

partial hepatectomy in mice. Hepatobiliary Surg Nutr 11 (2022)

199-211.

[67] K. Yang, J. Zhu, H.H. Luo, S.W. Yu, and L. Wang, Proprotein convertase subtilisin/kexin type 9 promotes intestinal tumor

development by activating Janus kinase 2/signal transducer and

activator of transcription 3/SOCS3 signaling in Apc(Min/+) mice.

Int J Immunopathol Pharmacol 35 (2021) 20587384211038345.

[68] W.X. Cheng, H. Huang, J.H. Chen, T.T. Zhang, G.Y.

Zhu, Z.T. Zheng, J.T. Lin, Y.P. Hu, Y. Zhang, X.L. Bai, Y. Wang,

Z.W. Xu, B. Song, Y.Y. Mao, F. Yang, and P. Zhang, Genistein

inhibits angiogenesis developed during rheumatoid arthritis

through the IL-6/JAK2/STAT3/VEGF signalling pathway. J

Orthop Translat 22 (2020) 92-100.

[69] L. Hong, Y. Lin, X. Yang, T. Wu, Y. Zhang, Z.

Xie, J. Yu, H. Zhao, G. Yi, and M. Fu, A Narrative Review of

STAT Proteins in Diabetic Retinopathy: From Mechanisms to

Therapeutic Prospects. Ophthalmol Ther 11 (2022) 2005-2026.


(19 摘要 Views, 107 PDF Downloads)

Refbacks

  • 当前没有refback。