Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-26T08:55:46.293Z Has data issue: false hasContentIssue false
  • English
  • Français

Role of the Wnt signalling pathway in the development of endothelial disorders in response to hyperglycaemia

Published online by Cambridge University Press:  04 December 2019

Martyna Durak-Kozica Open the ORCID record for Martyna Durak-Kozica [Opens in a new window] ,
Elżbieta Paszek  and
Ewa Ł Stępień
Martyna Durak-Kozica*
Affiliation:
Department of Medical Physics, Marian Smoluchowski Institute of Physics, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, Kraków, Poland
Elżbieta Paszek
Affiliation:
Clinical Department of Interventional Cardiology, John Paul II Hospital, Kraków, Poland
Ewa Ł Stępień
Affiliation:
Department of Medical Physics, Marian Smoluchowski Institute of Physics, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, Kraków, Poland
*
Author for correspondence: Martyna Durak-Kozica, E-mail: martyna.durak@doctoral.uj.edu.pl
Get access Rights & Permissions [Opens in a new window]

Abstract

Introduction

Diabetes mellitus (DM) is the most common metabolic disease. A WHO report from 2016 indicates that 422 million people worldwide suffer from DM or hyperglycaemia because of impaired glucose metabolism. Chronic hyperglycaemia leads to micro- and macrovessel damage, which may result in life-threatening complications. The Wnt pathway regulates cell proliferation and survival by modulating the expression of genes that control cell differentiation. Three linked Wnt pathways have been discovered thus far: a β-catenin-dependent pathway and two pathways independent of β-catenin – the planar cell polarity pathway and calcium-dependent pathway. The Wnt pathway regulates genes associated with inflammation, cell cycle, angiogenesis, fibrinolysis and other molecular processes.

Areas covered

This review presents the current state of knowledge regarding the contribution of the Wnt pathway to endothelial ageing under hyperglycaemic conditions and provides new insights into the molecular basis of diabetic endothelial dysfunction.

Conclusion

The β-catenin-dependent pathway is a potential target in the prophylaxis and treatment of early-stage diabetes-related vascular complications. However, the underlying molecular mechanisms remain largely undetermined and require further investigation.

Keywords

Endothelial cellshyperglycaemiaWnt pathway
Type
Unsolicited Review
Information
Expert Reviews in Molecular Medicine , Volume 21 , 2019 , e7
Copyright
Copyright © Cambridge University Press 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.vanHinsbergh, VWM (2012) Endothelium – role in regulation of coagulation and inflammation. Seminars in Immunopathology 34, 93–106.CrossRefGoogle Scholar
2.Palmer, RM et al. (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327, 524–526.CrossRefGoogle ScholarPubMed
3.Montoro-García, S et al. (2014) Potential value of targeting vonWillebrand factor in atherosclerotic cardiovascular disease. Expert Opinion on Therapeutic Targets 18, 43–53.CrossRefGoogle Scholar
4.Stegenga, ME et al. (2006) Hyperglycemia stimulates coagulation, whereas hyperinsulinemia impairs fibrinolysis in healthy humans. Diabetes 55, 1807–1812.CrossRefGoogle Scholar
5.Dogné, S et al. (2018) Endothelial glycocalyx as a shield against diabetic vascular complications: involvement of hyaluronan and hyaluronidases. Arteriosclerosis, Thrombosis, and Vascular Biology 38, 1427–1439.CrossRefGoogle Scholar
6.Popov, D (2010) Endothelial cell dysfunction in hyperglycemia: phenotypic change, intracellular signaling modification, ultrastructural alteration, and potential clinical outcomes. International Journal of Diabetes and Clinical Research 2, 189–195.Google Scholar
7.Laughlin, MH et al. (2008) Importance of hemodynamic forces as signals for exercise-induced changes in endothelial cell phenotype. Journal of Applied Physiology 104, 588–600.CrossRefGoogle Scholar
8.Cade, W (2008) Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Physical Therapy 88, 1322–1335.CrossRefGoogle Scholar
9.Funamoto, K et al. (2017) Endothelial monolayer permeability under controlled oxygen tension. Integrative Biology 9, 529–538.CrossRefGoogle ScholarPubMed
10.Hirose, A et al. (2010) Advanced glycation end products increase endothelial permeability through the RAGE/Rho signaling pathway. FEBS Letters 584, 61–66.CrossRefGoogle ScholarPubMed
11.Rho, SS et al. (2017) Dynamic regulation of vascular permeability by vascular endothelial cadherin-mediated endothelial cell-cell junction. Journal of Nippon Medical School 84, 148–159.CrossRefGoogle Scholar
12.Fraisl, P et al. (2009) Regulation of angiogenesis by oxygen and metabolism. Developmental Cell 16, 167–179.CrossRefGoogle Scholar
13.Mundi, S et al. (2018) Endothelial permeability, LDL, deposition, and cardiovascular risk factors-a review. Cardiovascular Research 114, 34–52.CrossRefGoogle ScholarPubMed
14.Avogadro, A et al. (2011) Endothelial dysfunction in diabetes: the role of reparatory mechanisms. Diabetes Care 34, 285–290.CrossRefGoogle Scholar
15.Brunssen, C et al. (2010) COUP-TFIIis regulated by high glucose in endothelial cells. Hormone and Metabolic Research 42, 189–195.CrossRefGoogle ScholarPubMed
16.Williams, SB et al. (1998) Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo. Circulation 97, 1695–1701.CrossRefGoogle ScholarPubMed
17.David, L et al. (2008) Bone morphogenetic protein-9 is a vascular quiescence factor. Circulation Research 102, 914–922.CrossRefGoogle ScholarPubMed
18.Tanaka, A et al. (2010) Inhibition of endothelial cell activation by bHLH protein E2-2 and its impairment of angiogenesis. Blood 115, 4138–4147.CrossRefGoogle Scholar
19.Singh, H et al. (2010) High glucose and elevated fatty acids suppress signaling by the endothelium protective ligand angiopoietin-1. Microvascular Research 79, 121–127.CrossRefGoogle ScholarPubMed
20.Fukuhara, S et al. (2010) Angiopoietin-1/Tie2 receptor signaling in vascular quiescence and angiogenesis. Histology & Histopathology 25, 387–396.Google Scholar
21.Jiang, A et al. (2009) Loss of VLDL receptor activates retinal vascular endothelial cells and promotes angiogenesis. Investigative Ophthalmology & Visual Science 50, 844–850.CrossRefGoogle ScholarPubMed
22.Xu, L et al. (2009) Promoter cloning and characterization of the anti-vascular proliferation gene R-ras. Role of ETS- and SP-binding motifs. Journal of Biological Chemistry 284, 2706–2718.CrossRefGoogle ScholarPubMed
23.Rajapakse, AG et al. (2009) The hexosamine biosynthesis inhibitor azaserine prevents endothelial inflammation and dysfunction under hyperglycemic condition through antioxidant effects. The American Journal of Physiology-Heart and Circulatory Physiology 296, 815–822.CrossRefGoogle ScholarPubMed
24.Liu, Y et al. (2009) Effect of diabetes duration and high glucose on retinal interleukin-1b expression. Investigative Ophthalmology & Visual Science 50, 4984. E-Abstract.Google Scholar
25.Bhatwadekar, AD et al. (2009) Retinal endothelial cell apoptosis stimulates recruitment of endothelial progenitor cells. Investigative Ophthalmology & Visual Science 50, 4967–4973.CrossRefGoogle ScholarPubMed
26.Shakhov, AS et al. (2014) Reorganization of endothelial cells cytoskeleton during formation of functional monolayer in vitro. Cell and Tissue Biology 8, 138–151.CrossRefGoogle Scholar
27.Targosz-Korecka, M et al. (2013) Stiffness memory of EA.hy926 endothelial cells in response to chronic hyperglycemia. Cardiovascular Diabetology 12, 96.CrossRefGoogle ScholarPubMed
28.Sharma, A et al. (2017) The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activator dh404 protects against diabetes-induced endothelial dysfunction. Cardiovascular Diabetology 16, 33.CrossRefGoogle ScholarPubMed
29.Bucciarelli, LG et al. (2009) Inflammatory stress in primary venous and aortic endothelial cells of type 1 diabetic mice. Diabetes & Vascular Disease Research 6, 249–261.CrossRefGoogle Scholar
30.Popov, D et al. (2006) Cellular mechanisms and signalling pathways activated by high glucose and AGE-albumin in the aortic endothelium. Archives of Physiology and Biochemistry 112, 265–273.CrossRefGoogle ScholarPubMed
31.Trudeau, K et al. (2009) High glucose alters mitochondrial morphology and membrane potential heterogeneity in retinal endothelial cells. Investigative Ophthalmology & Visual Science 50, 33. E-Abstract.Google Scholar
32.Dokken, BB (2008) The pathophysiology of cardiovascular disease and diabetes: beyond blood pressure and lipids. Diabetes Spectrum 21, 160–165.CrossRefGoogle Scholar
33.Klaassen, I et al. (2013) Molecular basis of the inner blood-retinal barrier and its breakdown in diabetic macular edema and other pathological conditions. Progress in Retinal and Eye Research 34, 19–48.CrossRefGoogle Scholar
34.Naka, K et al. (2012) Determinants of vascular function in patients with type 2 diabetes. Cardiovascular Diabetology 11, 127.CrossRefGoogle Scholar
35.Reddy, MA et al. (2015) Epigenetic mechanisms in diabetic complications and metabolic memory. Diabetologia 58, 443–455.CrossRefGoogle ScholarPubMed
36.Sánchez-Duffhues, G et al. (2018) Endothelial-to-mesenchymal transition in cardiovascular diseases: developmental signaling pathways gone awry. Developmental Dynamics 247, 492–508.CrossRefGoogle ScholarPubMed
37.Van Meeteren, LA et al. (2012) Regulation of endothelial cell plasticity by TGF-β. Cell and Tissue Research 347, 177–186.CrossRefGoogle Scholar
38.Chen, Q et al. (2016) Endothelial cells are progenitors of cardiac pericytes and vascular smooth muscle cells. Nature Communications 7, 12422.CrossRefGoogle ScholarPubMed
39.Li, J et al. (2009) Endothelial-myofibroblast transition contributes to the early development of diabetic renal interstitial fibrosis in streptozotocin-induced diabetic mice. The American Journal of Pathology 175, 1380–1388.CrossRefGoogle ScholarPubMed
40.Widyantoro, B et al. (2010) Endothelial cell-derived endothelin-1 promotes cardiac fibrosis in diabetic hearts through stimulation of endothelial-to-mesenchymal transition. Circulation 175, 1380–1388.Google Scholar
41.Aronson, D et al. (2002) How hyperglycemia promotes atherosclerosis: molecular mechanisms. Cardiovascular Diabetology 1, 1–10.CrossRefGoogle ScholarPubMed
42.Wu, X et al. (2017) Exosomes from high glucose-treated glomerular endothelial cells trigger the epithelial-mesenchymal transition and dysfunction of podocytes. Scientific Reports 7, 9371.CrossRefGoogle ScholarPubMed
43.Korinek, V et al. (1998) Two members of the Tcf family implicated in Wnt/beta-catenin signaling during embryogenesis in the mouse. Molecular and Cellular Biology 18, 1248–1256.CrossRefGoogle ScholarPubMed
44.Lowry, WE et al. (2005) Defining the impact of beta-catenin/Tcf transactivation on epithelial stem cells. Genes & Development 19, 1596–1611.CrossRefGoogle ScholarPubMed
45.Fahiminiya, S et al. (2013) Mutations in WNT1 are a cause of osteogenesis imperfecta. Journal of Medical Genetics 50, 345–348.CrossRefGoogle ScholarPubMed
46.Chen, AE et al. (2005) Protein kinase A signalling via CREB controls myogenesis induced by Wnt proteins. Nature 433, 317–322.CrossRefGoogle ScholarPubMed
47.Kanazawa, A et al. (2004) Association of the gene encoding wingless-type mammary tumor virus integration-site family member 5B (WNT5B) with type 2 diabetes. American Journal of Human Genetics 75, 832–843.CrossRefGoogle ScholarPubMed
48.Christodoulides, C et al. (2006) WNT10B mutations in human obesity. Diabetologia 49, 678–684.CrossRefGoogle ScholarPubMed
49.Habas, R et al. (2005) Dishevelled and Wnt signaling: is the nucleus the final frontier? The Journal of Biology 4, 2.CrossRefGoogle ScholarPubMed
50.Dessimoz, J et al. (2005) Pancreas-specific deletion of β-catenin reveals Wnt-dependent and Wnt-independent functions during development. Current Biology 15, 1677–1683.CrossRefGoogle ScholarPubMed
51.Schinner, S et al. (2008) Regulation of insulin secretion, glucokinase gene transcription and beta cell proliferation by adipocyte-derived Wnt signalling molecules. Diabetologia 51, 147–154.CrossRefGoogle ScholarPubMed
52.Rulifson, IC et al. (2007) Wnt signaling regulates pancreatic β cell proliferation. Proceedings of the National Academy of Sciences of the USA 104, 6247–6252.CrossRefGoogle ScholarPubMed
53.Liu, Z et al. (2009) Stromal cell-derived factor-1 promotes survival of pancreatic beta cells by the stabilization of beta-catenin and activation of transcription factor 7-like 2 (TCF7L2). Diabetologia 52, 1589–1598.CrossRefGoogle Scholar
54.Fujino, T et al. (2003) Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion. Proceedings of the National Academy of Sciences of the USA 100, 229–234.CrossRefGoogle ScholarPubMed
55.Liu, Z et al. (2008) Glucagon-like peptide-1 activation of TCF7L2-dependent Wnt signaling enhances pancreatic b cell proliferation. Journal of Biological Chemistry 283, 8723–8735.CrossRefGoogle Scholar
56.Cheng, CW et al. (2003) Wnt-1 signaling inhibits human umbilical vein endothelial cell proliferation and alters cell morphology. Experimental Cell Research 291, 415–425.CrossRefGoogle ScholarPubMed
57.Choi, HJ et al. (2012) The Wnt pathway and the roles for its antagonists, Dkks, in angiogenesis. Life 64, 724–731.Google ScholarPubMed
58.Mao, C et al. (2000) Differential expression of rat frizzled-related frzb-1 and frizzled receptor fz1 and fz2 genes in the rat aorta after balloon injury. Arteriosclerosis, Thrombosis, and Vascular Biology 20, 43–51.CrossRefGoogle ScholarPubMed
59.Goodwin, AM et al. (2006) Cultured endothelial cells display endogenous activation of the canonical Wnt signaling pathway and express multiple ligands, receptors, and secreted modulators of Wnt signaling. Developmental Dynamics 235, 3110–3120.CrossRefGoogle ScholarPubMed
60.Anagnostou, SH et al. (2008) Glucose induces an autocrine activation of the Wnt/β-catenin pathway in macrophage cell lines. Biochemical Journal 416, 211–218.CrossRefGoogle ScholarPubMed
61.Komiya, Y et al. (2008) Wnt signal transduction pathways. Organogenesis 4, 68–75.CrossRefGoogle ScholarPubMed
62.Minde, DP et al. (2011) Messing up disorder: how do missense mutations in the tumor suppressor protein APC lead to cancer? Molecular Cancer 10, 101.CrossRefGoogle Scholar
63.Chandramouli, A et al. (2013) Gli activity is critical at multiple stages of embryonic mammary and nipple development. PLoS ONE 8, e79845.CrossRefGoogle ScholarPubMed
64.Jho, E et al. (2002) Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Molecular and Cellular Biology 22, 1172–1183.CrossRefGoogle Scholar
65.Christodoulides, C et al. (2006) The Wnt antagonist Dickkopf-1 and its receptors are coordinately regulated during early human adipogenesis. Journal of Cell Science 119, 2613–2620.CrossRefGoogle ScholarPubMed
66.Cawthorn, WP et al. (2007) Tumour necrosis factor-alpha inhibits adipogenesis via a beta-catenin/TCF4(TCF7L2)-dependent pathway. Cell Death & Differentiation 14, 1361–1373.CrossRefGoogle Scholar
67.Haidari, M et al. (2014) Disruption of endothelial adherens junctions by high glucose is mediated by protein kinase C-β-dependent vascular endothelial cadherin tyrosine phosphorylation. Cardiovascular Diabetology 13, 105.CrossRefGoogle ScholarPubMed
68.Lee, K et al. (2012) Therapeutic potential of a monoclonal antibody blocking the Wnt pathway in diabetic retinopathy. Diabetes 61, 2948–2957.CrossRefGoogle ScholarPubMed
69.Holnthoner, W et al. (2002) Fibroblast growth factor-2 induces Lef/Tcf-dependent transcription in human endothelial cells. Journal of Biological Chemistry 277, 45847–45853.CrossRefGoogle ScholarPubMed
70.Gelfand, BD et al. (2011) Hemodynamic activation of beta-catenin and T-cell-specific transcription factor signaling in vascular endothelium regulates fibronectin expression. Arteriosclerosis, Thrombosis, and Vascular Biology 31, 1625–1633.CrossRefGoogle ScholarPubMed
71.Hou, N et al. (2016) Transcription factor 7-like 2 mediates canonical Wnt/β-Catenin signaling and c-myc upregulation in heart failure. Circulation: Heart Failure 9, 1–18. doi: 10.1161/CIRCHEARTFAILURE.116.003010 e003010.Google ScholarPubMed
72.Cesare, AJ et al. (2010) Alternative lengthening of telomeres. Models, mechanisms, and implications. Nature Reviews Genetics 11, 319–330.CrossRefGoogle ScholarPubMed
73.Bilsland, AE et al. (2006) Transcriptional repression of telomerase RNA gene expression by c-Jun-NH2-kinase and Sp1/Sp3. Cancer Research 66, 1363–1370.CrossRefGoogle ScholarPubMed
74.Deng, WG et al. (2007) Tumor-specific activation of human telomerase reverses transcriptase promoter activity by activating enhancer-binding protein-2β in human lung cancer cells. Journal of Biological Chemistry 282, 26460–26470.CrossRefGoogle ScholarPubMed
75.Zhang, Y et al. (2012) Human Telomerase Reverse Transcriptase (hTERT) is a novel target of the Wnt/β-catenin pathway in human cancer. Journal of Biological Chemistry 289, 32494–32511.CrossRefGoogle Scholar
76.Park, JI et al. (2009) Telomerase modulates Wnt signalling by association with target gene chromatin. Nature 460, 66–72.CrossRefGoogle ScholarPubMed
77.Khandekar, MJ et al. (2011) Molecular mechanisms of cancer development in obesity. Nature Reviews Cancer 11, 886–895.CrossRefGoogle ScholarPubMed
78.Chocarro-Calvo, A et al. (2013) Glucose-induced β-catenin acetylation enhances Wnt signaling in cancer. Molecular Cell 49, 474–486.CrossRefGoogle Scholar
79.Chouhan, S et al. (2016) Glucose induced activation of canonical Wnt signaling pathway in hepatocellular carcinoma is regulated by DKK4. Scientific Reports 6, 27558.CrossRefGoogle ScholarPubMed
80.Coughlin, SS et al. (2004) Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults. American Journal of Epidemiology 159, 1160–1167.CrossRefGoogle Scholar
81.Jee, SH et al. (2005) Fasting serum glucose level and cancer risk in Korean men and women. Journal of the American Medical Association 293, 194–202.CrossRefGoogle ScholarPubMed
82.Baron, JA et al. (2001) Metabolic disorders and breast cancer risk (United States). Cancer Causes and Control 12, 875–880.CrossRefGoogle Scholar
83.Lipscombe, LL et al. (2006) Diabetes mellitus and breast cancer: a retrospective population-based cohort study. Breast Cancer Research and Treatment 98, 349–356.CrossRefGoogle ScholarPubMed
84.Wideroff, L et al. (1997) Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. Journal of the National Cancer Institute 89, 1360–1365.CrossRefGoogle Scholar
85.Friberg, E et al. (2007) Diabetes mellitus and risk of endometrial cancer: a meta-analysis. Diabetologia 50, 1365–1374.CrossRefGoogle ScholarPubMed
86.Anderson, KE et al. (2001) Diabetes and endometrial cancer in the Iowa Women's Health Study. Cancer Epidemiology Biomarkers and Prevention 10, 611–616.Google ScholarPubMed
87.Vigneri, P et al. (2009) Diabetes and cancer. Endocrine-Related Cancer 16, 1103–1123.CrossRefGoogle ScholarPubMed
88.Yun, J et al. (2009) Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science 325, 1555–1559.CrossRefGoogle ScholarPubMed
89.Tseng, CH et al. (2009) Age-related risk of mortality from bladder cancer in diabetic patients: a 12-year follow-up of a national cohort in Taiwan. Annals of Medicine 41, 371–379.CrossRefGoogle ScholarPubMed
90.Lewis, JD et al. (2011) Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study. Diabetes Care 34, 916–922.CrossRefGoogle ScholarPubMed
91.Masur, K et al. (2011) Diabetogenic glucose and insulin concentrations modulate transcriptom and protein levels involved in tumour cell migration, adhesion and proliferation. British Journal of Cancer 104, 345–352.CrossRefGoogle Scholar
92.Harding, JL et al. (2015) Cancer risk among people with type 1 and type 2 diabetes: disentangling true associations, detection bias, and reverse causation. Diabetes Care 38, 264–270.CrossRefGoogle ScholarPubMed
93.Yan, HY et al. (2018) TUG1 promotes diabetic atherosclerosis by regulating proliferation of endothelial cells via Wnt pathway. The European Review for Medical and Pharmacological 22, 6922–6929.Google ScholarPubMed
94.Kim, J et al. (2010) Wnt5a induces endothelial inflammation via beta-catenin-independent signaling. Journal of Immunology 185, 1274–1282.CrossRefGoogle ScholarPubMed
95.Christman, MA et al. (2008) Wnt5a is expressed in murine and human atherosclerotic lesions. American Journal of Physiology. Heart and Circulatory Physiology 294, 2864–2870.CrossRefGoogle ScholarPubMed
96.Bhatt, PM et al. (2012) Increased Wnt5a mRNA expression in advanced atherosclerotic lesions, and oxidized LDL treated human monocyte-derived macrophages. The Open Circulation & Vascular Journal 5, 1–7.CrossRefGoogle ScholarPubMed
97.Malgor, R et al. (2014) Wnt5a, TLR2 and TLR4 are elevated in advanced human atherosclerotic lesions. Inflammation Research 63, 277–285.CrossRefGoogle ScholarPubMed
98.Laeremans, H et al. (2011) Blocking of frizzled signaling with a homologous peptide fragment of wnt3a/wnt5a reduces infarct expansion and prevents the development of heart failure after myocardial infarction. Circulation 124, 1626–1635.CrossRefGoogle ScholarPubMed
99.Dejana, E et al. (2008) The role of adherens junctions and VE-cadherin in the control of vascular permeability. Journal of Cell Science 121, 2115–2122.CrossRefGoogle ScholarPubMed
100.Schulte, D et al. (2011) Stabilizing the VE-cadherin-catenin complex blocks leukocyte extravasation and vascular permeability. EMBO Journal 30, 4157–4170.CrossRefGoogle ScholarPubMed
101.Behzadian, MA et al. (2003) VEGF-induced paracellular permeability in cultured endothelial cells involves urokinase and its receptor. FASEB Journal 17, 753–754.CrossRefGoogle ScholarPubMed
102.Esser, S et al. (1998) Vascular endothelial growth factor induces VE-cadherin tyrosine phosphorylation in endothelial cells. Journal of Cell Science 111, 1853–1865.Google ScholarPubMed
103.Goldberg, RB (2009) Cytokine and cytokine-like inflammation markers, endothelial dysfunction, and imbalanced coagulation in development of diabetes and its complications. The Journal of Clinical Endocrinology and Metabolism 94, 3171–3182.CrossRefGoogle ScholarPubMed
104.Chen, C et al. (2016) Tanshinol suppresses endothelial cells apoptosis in mice with atherosclerosis via lncRNA TUG1up-regulating the expression of miR-26a. American Journal of Translational Research 8, 2981–2991.Google ScholarPubMed
105.Ueland, T et al. (2009) Dickkopf-1 enhances inflammatory interaction between platelets and endothelial cells and shows increased expression in atherosclerosis. Arteriosclerosis Thrombosis and Vascular Biology 29, 1228–1234.CrossRefGoogle ScholarPubMed
106.Lattanzio, S et al. (2014) Circulating dickkopf-1 in diabetes mellitus: association with platelet activation and effects of improved metabolic control and low-dose aspirin. Journal of the American Heart Association 3, 1–10. doi: 10.1161/JAHA.114.001000.CrossRefGoogle ScholarPubMed
107.Klein, BEK et al. (2009) The relation of markers of inflammation and endothelial dysfunction to the prevalence and progression of diabetic retinopathy: Wisconsin epidemiologic study of diabetic retinopathy. Archives of Ophthalmology 127, 1175–1182.CrossRefGoogle ScholarPubMed
108.van Hecke, MV et al. (2005) Inflammation and endothelial dysfunction are associated with retinopathy: the Hoorn Study. Diabetologia 48, 1300–1306.CrossRefGoogle ScholarPubMed
109.Chen, Y et al. (2009) Activation of the Wnt pathway plays a pathogenic role in diabetic retinopathy in humans and animal models. The American Journal of Pathology 175, 2676–2685.CrossRefGoogle Scholar
110.Zhou, KK et al. (2014) Interruption of Wnt signaling in Müller cells ameliorates ischemia-induced retinal neovascularization. PLoS ONE 9, e108454.CrossRefGoogle ScholarPubMed
111.Mazzoni, J et al. (2017) The Wnt inhibitor Apcdd1 coordinates vascular remodeling and barrier maturation of retinal blood vessels. Neuron 96, 1055–1069.CrossRefGoogle ScholarPubMed
112.Zhang, B et al. (2010) Inhibition of connective tissue growth factor overexpression in diabetic retinopathy by SERPINA3 K via blocking the WNT/beta-catenin pathway. Diabetes 59, 1809–1816.CrossRefGoogle Scholar
113.Hülsken, J et al. (1994) E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton. Journal of Cell Biology 127, 2061–2069.CrossRefGoogle ScholarPubMed
114.Orsulic, S et al. (1999) E-cadherin binding prevents beta-catenin nuclear localization and beta-catenin/LEF-1-mediated transactivation. Journal of Cell Science 112, 1237–1245.Google ScholarPubMed
115.McMahon, AP et al. (1989) Ectopic expression of the proto-oncogene int-1 in Xenopus embryos leads to duplication of the embryonic axis. Cell 58, 1075–1084.CrossRefGoogle ScholarPubMed
116.Cox, RT et al. (1996) Armadillo is required for adherens junction assembly, cell polarity, and morphogenesis during Drosophila embryogenesis. Journal of Cell Biology 134, 133–148.CrossRefGoogle ScholarPubMed
117.Kam, Y et al. (2009) Cadherin-bound beta-catenin feeds into the Wnt pathway upon adherens junctions dissociation: evidence for an intersection between beta-catenin pools. PLoS ONE 4, e4580.CrossRefGoogle ScholarPubMed
118.Eger, A et al. (2000) Epithelial mesenchymal transition by c-Fos estrogen receptor activation involves nuclear translocation of beta-catenin and upregulation of beta-catenin/lymphoid enhancer binding factor-1 transcriptional activity. Journal of Cell Biology 148, 173–188.CrossRefGoogle ScholarPubMed
119.Aljada, A et al. (2012) Metformin and neoplasia: implications and indications. Pharmacology & Therapeutics 133, 108–115.CrossRefGoogle ScholarPubMed
120.Zhao, X et al. (2015) Aldehyde dehydrogenase-2 protects against myocardial infarction-related cardiac fibrosis through modulation of the Wnt/β-catenin signaling pathway. Therapeutics and Clinical Risk Management 11, 1371–1381.CrossRefGoogle ScholarPubMed
121.Gurney, A et al. (2012) Wnt pathway inhibition via the targeting of frizzled receptors results in decreased growth and tumorigenicity of human tumors. PNAS 109, 11717–11722.CrossRefGoogle ScholarPubMed
122.Lee, HJ et al. (2015) Structure-based discovery of novel small molecule Wnt signaling inhibitors by targeting the cysteine-rich domain of frizzled. Journal of Biological Chemistry 290, 30596–30606.CrossRefGoogle ScholarPubMed
123.Ryan, DG et al. (2006) MicroRNAs of the mammalian eye display distinct and overlapping tissue specificity. Molecular Vision 12, 1175–1184.Google ScholarPubMed
124.Takahashi, Y et al. (2015) MicroRNA-184 modulates canonical Wnt signaling through the regulation of frizzled-7 expression in the retina with ischemia-induced neovascularization. FEBS Letters 589, 1143–1149.CrossRefGoogle ScholarPubMed
125.Shen, J et al. (2008) MicroRNAs regulate ocular neovascularization. Molecular Therapy 16, 1208–1216.CrossRefGoogle ScholarPubMed