Identification of novel proliferative diabetic retinopathy related genes on protein-protein interaction network

Proliferative diabetic retinopathy (PDR) is an eye disease caused by diabetes. Because this disease may lead to blindness, effective treatments are urgently needed. However, the pathogenesis is far from good understanding, resulting in difficulties in designing effective treatments. In this study, we tried to give a few contributions to uncover its pathogenesis by searching for novel PDR-related genes. New genes were identified based on known genes related to proliferative diabetic retinopathy using a proteinprotein interaction network with a shortest path approach. The newly identified genes were further filtered using a permutation test. The analyses showed that the discovered genes were highly enriched in gene ontology terms and KEGG pathways shared by known proliferative diabetic retinopathy related genes. Finally, we discussed the likelihood of some newly discovered genes being novel genes related to proliferative diabetic retinopathy.

[1]  Lois E. H. Smith,et al.  Oligodeoxynucleotides inhibit retinal neovascularization in a murine model of proliferative retinopathy. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Anna-Katharina Müller,et al.  FGF receptors 1 and 2 are key regulators of keratinocyte migration in vitro and in wounded skin , 2012, Journal of Cell Science.

[3]  N. Sarvetnick,et al.  Transgenic mice expressing IFN-gamma in the retina develop inflammation of the eye and photoreceptor loss. , 1994, Investigative ophthalmology & visual science.

[4]  Jennifer I. Lim,et al.  A COMPARISON OF HYPOXIA-INDUCIBLE FACTOR-α IN SURGICALLY EXCISED NEOVASCULAR MEMBRANES OF PATIENTS WITH DIABETES COMPARED WITH IDIOPATHIC EPIRETINAL MEMBRANES IN NONDIABETIC PATIENTS , 2010, Retina.

[5]  Timothy S Kern,et al.  Role of nitric oxide, superoxide, peroxynitrite and PARP in diabetic retinopathy. , 2009, Frontiers in bioscience.

[6]  Lei Chen,et al.  Prediction of human genes' regulatory functions based on proteinprotein interaction network. , 2012, Protein and peptide letters.

[7]  R. Paschke,et al.  Relation between glycaemic control, hyperinsulinaemia and plasma concentrations of soluble adhesion molecules in patients with impaired glucose tolerance or Type II diabetes , 2002, Diabetologia.

[8]  Damian Szklarczyk,et al.  The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored , 2010, Nucleic Acids Res..

[9]  Zhihong Zhou,et al.  Vascular endothelial growth factor gene expression regulated by protein kinase C pathway in endothelial cells during hypoxia. , 2002, Hang tian yi xue yu yi xue gong cheng = Space medicine & medical engineering.

[10]  Anna Lipińska,et al.  Increased interleukin-18 content and angiogenic activity of sera from diabetic (Type 2) patients with background retinopathy. , 2005, Journal of diabetes and its complications.

[11]  Kui Zhang,et al.  Prediction of protein function using protein-protein interaction data , 2002, Proceedings. IEEE Computer Society Bioinformatics Conference.

[12]  Alan Wells,et al.  IP-10 induces dissociation of newly formed blood vessels , 2009, Journal of Cell Science.

[13]  G. Slama,et al.  Taq I polymorphism of the vitamin D receptor and risk of severe diabetic retinopathy , 2002, Diabetologia.

[14]  Yoshinori Mitamura,et al.  Macrophage migration inhibitory factor levels in the vitreous of patients with proliferative diabetic retinopathy , 2000, The British journal of ophthalmology.

[15]  Yongjin Li,et al.  Discovering disease-genes by topological features in human protein-protein interaction network , 2006, Bioinform..

[16]  D McLeod,et al.  Retinal and preretinal localisation of epidermal growth factor, transforming growth factor alpha, and their receptor in proliferative diabetic retinopathy. , 1994, The British journal of ophthalmology.

[17]  Chun-Wei Tung,et al.  Acquiring Decision Rules for Predicting Ames-Negative Hepatocarcinogens Using Chemical-Chemical Interactions , 2014, PRIB.

[18]  J. Van Damme,et al.  Autocrine CCL2, CXCL4, CXCL9 and CXCL10 signal in retinal endothelial cells and are enhanced in diabetic retinopathy. , 2013, Experimental eye research.

[19]  Enrique Cervera,et al.  IL-2 and IFN-gamma in the retina of diabetic rats , 2010, Graefe's Archive for Clinical and Experimental Ophthalmology.

[20]  S. Doğanay,et al.  Adrenomedullin and Leptin Levels in Diabetic Retinopathy and Retinal Diseases , 2005, Ophthalmologica.

[21]  Daniel Petrovič,et al.  Candidate Genes for Proliferative Diabetic Retinopathy , 2013, BioMed research international.

[22]  Yu-Dong Cai,et al.  Finding Candidate Drugs for Hepatitis C Based on Chemical-Chemical and Chemical-Protein Interactions , 2014, PloS one.

[23]  B. Liu,et al.  Identification of Real MicroRNA Precursors with a Pseudo Structure Status Composition Approach , 2015, PloS one.

[24]  J. Rosenbaum,et al.  Soluble forms of EphrinB2 and EphB4 reduce retinal neovascularization in a model of proliferative retinopathy. , 2005, Investigative ophthalmology & visual science.

[25]  Hidehiro Ishii,et al.  Vascular Endothelial Growth Factor–Induced Retinal Permeability Is Mediated by Protein Kinase C In Vivo and Suppressed by an Orally Effective β-Isoform–Selective Inhibitor , 1997, Diabetes.

[26]  Z. Makita,et al.  Increased Levels of Vascular Endothelial Growth Factor and Advanced Glycation End Products in Aqueous Humor of Patients With Diabetic Retinopathy , 2001, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[27]  J. Spranger,et al.  Growth Factor Alterations in Advanced Diabetic Retinopathy: A Possible Role of Blood Retina Barrier Breakdown , 1997, Diabetes.

[28]  Mohsen Rezaeian,et al.  Expression of CC chemokines CCL2, CCL5, and CCL11 is associated with duration of disease and complications in type-1 diabetes: a study on Iranian diabetic patients. , 2013, Clinical laboratory.

[29]  Yosuf El-Shabrawi,et al.  Multiplex bead analysis of vitreous and serum concentrations of inflammatory and proangiogenic factors in diabetic patients , 2008, Molecular vision.

[30]  Beverly A. Teicher,et al.  Antiangiogenic effects of a protein kinase Cβ-selective small molecule , 2001, Cancer Chemotherapy and Pharmacology.

[31]  M. Matsumura,et al.  Unbalanced vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor in diabetic retinopathy. , 2002, American journal of ophthalmology.

[32]  Yan Yu,et al.  Antifibrotic role of chemokine CXCL9 in experimental chronic pancreatitis induced by trinitrobenzene sulfonic acid in rats. , 2013, Cytokine.

[33]  H P Heidenkummer,et al.  [Recurrent vitreoretinal membranes in intravitreal silicon oil tamponade. Morphologic and immunohistochemical studies]. , 1996, Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft.

[34]  P. Campochiaro,et al.  Growth factor responsiveness of human retinal pigment epithelial cells. , 1990, Investigative ophthalmology & visual science.

[35]  E S Gragoudas,et al.  Inhibition of vascular endothelial growth factor prevents retinal ischemia-associated iris neovascularization in a nonhuman primate. , 1996, Archives of ophthalmology.

[36]  Limsoon Wong,et al.  Exploiting indirect neighbours and topological weight to predict protein function from protein--protein interactions , 2006 .

[37]  J. Klarlund,et al.  Hepatocyte growth factor induces epithelial cell motility through transactivation of the epidermal growth factor receptor. , 2007, Experimental cell research.

[38]  V. Reppucci,et al.  Soluble cellular adhesion molecules in proliferative vitreoretinopathy and proliferative diabetic retinopathy. , 1999, Current eye research.

[39]  Ke-Ping Xu,et al.  Cross talk between c-Met and epidermal growth factor receptor during retinal pigment epithelial wound healing. , 2007, Investigative ophthalmology & visual science.

[40]  Hideo Sakamoto,et al.  Inhibition of pulmonary fibrosis by the chemokine IP-10/CXCL10. , 2004, American journal of respiratory cell and molecular biology.

[41]  F. Doran,et al.  Interleukin (IL)-6, Interleukin (IL)-8 Levels and Cellular Composition of the Vitreous Humor in Proliferative Diabetic Retinopathy, Proliferative Vitreoretinopathy, and Traumatic Proliferative Vitreoretinopathy , 2005, Ocular immunology and inflammation.

[42]  Lee M Ellis,et al.  Regulatory role of c-Met in insulin-like growth factor-I receptor–mediated migration and invasion of human pancreatic carcinoma cells , 2006, Molecular Cancer Therapeutics.

[43]  A. Eid,et al.  Nox4 NAD(P)H Oxidase Mediates Src-dependent Tyrosine Phosphorylation of PDK-1 in Response to Angiotensin II , 2008, Journal of Biological Chemistry.

[44]  Xiaolong Wang,et al.  miRNA-dis: microRNA precursor identification based on distance structure status pairs. , 2015, Molecular bioSystems.

[45]  Rajmund Adamiec,et al.  [Selected problems of endothelial functions. I. The role of endothelium in maintaining the hematological and circulatory balance]. , 2002, Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego.

[46]  M. Burdick,et al.  IFN-gamma-inducible protein-10 attenuates bleomycin-induced pulmonary fibrosis via inhibition of angiogenesis. , 1999, Journal of immunology.

[47]  S Kinoshita,et al.  Overexpression of matrix metalloproteinase-10 and matrix metalloproteinase-3 in human diabetic corneas: a possible mechanism of basement membrane and integrin alterations. , 2001, The American journal of pathology.

[48]  G Chatellier,et al.  Contribution of genetic polymorphism in the renin-angiotensin system to the development of renal complications in insulin-dependent diabetes: Genetique de la Nephropathie Diabetique (GENEDIAB) study group. , 1997, The Journal of clinical investigation.

[49]  S. Kasif,et al.  Whole-genome annotation by using evidence integration in functional-linkage networks. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[50]  Jia Qu,et al.  Involvement of PI3K/Akt signaling pathway in hepatocyte growth factor-induced migration of uveal melanoma cells. , 2008, Investigative ophthalmology & visual science.

[51]  Kyong Soo Park,et al.  Differential Expression of Vitreous Proteins in Proliferative Diabetic Retinopathy , 2006, Current eye research.

[52]  Frank Petersen,et al.  Molecular pathways of platelet factor 4/CXCL4 signaling. , 2011, European journal of cell biology.

[53]  T. Aw,et al.  Endothelial Cells Exposed to Anoxia/Reoxygenation Are Hyperadhesive to T‐lymphocytes: Kinetics and Molecular Mechanisms , 2000, Microcirculation.

[54]  J. Erusalimsky,et al.  Basic fibroblast growth factor upregulates the expression of vascular endothelial growth factor in vascular smooth muscle cells. Synergistic interaction with hypoxia. , 1995, Circulation.

[55]  Borna Mehrad,et al.  Chemokines as mediators of tumor angiogenesis and neovascularization. , 2011, Experimental cell research.

[56]  J. Padbury,et al.  A Novel Phosphoinositide 3-Kinase-dependent Pathway for Angiotensin II/AT-1 Receptor-mediated Induction of Collagen Synthesis in MES-13 Mesangial Cells* , 2007, Journal of Biological Chemistry.

[57]  Ka-Lok Ng,et al.  Prediction of protein functions based on function-function correlation relations , 2010, Comput. Biol. Medicine.

[58]  M. Brownlee Biochemistry and molecular cell biology of diabetic complications , 2001, Nature.

[59]  Esther J. Kuiper,et al.  The Angio-Fibrotic Switch of VEGF and CTGF in Proliferative Diabetic Retinopathy , 2008, PloS one.

[60]  Timothy J. Yeatman,et al.  A renaissance for SRC , 2004, Nature Reviews Cancer.

[61]  M. Matsumura,et al.  Expression of Pigment Epithelium-Derived Factor and Vascular Endothelial Growth Factor in Fibrovascular Membranes from Patients with Proliferative Diabetic Retinopathy , 2006, Japanese Journal of Ophthalmology.

[62]  Christopher J. Robinson,et al.  The splice variants of vascular endothelial growth factor (VEGF) and their receptors. , 2001, Journal of cell science.

[63]  R. Simó,et al.  Vitreous levels of IGF-I, IGF binding protein 1, and IGF binding protein 3 in proliferative diabetic retinopathy: a case-control study. , 2000, Diabetes care.

[64]  Ulrich Schraermeyer,et al.  A central role for inflammation in the pathogenesis of diabetic retinopathy , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[65]  Karl Hormann,et al.  Effect of the abrogation of TGF-beta1 by antisense oligonucleotides on the expression of TGF-beta-isoforms and their receptors I and II in isolated fibroblasts from keloid scars. , 2010, International journal of molecular medicine.

[66]  Junjie Chen,et al.  Pse-in-One: a web server for generating various modes of pseudo components of DNA, RNA, and protein sequences , 2015, Nucleic Acids Res..

[67]  K. Matsushima,et al.  International union of pharmacology. XXII. Nomenclature for chemokine receptors. , 2000, Pharmacological reviews.

[68]  A. Ljubimov,et al.  Effects of angiogenic growth factor combinations on retinal endothelial cells. , 2002, Experimental eye research.

[69]  Thomas A Einhorn,et al.  Chemokine expression is upregulated in chondrocytes in diabetic fracture healing. , 2013, Bone.

[70]  Luc Missotten,et al.  Expression of hypoxia-inducible factor-1α and the protein products of its target genes in diabetic fibrovascular epiretinal membranes , 2007, British Journal of Ophthalmology.

[71]  V P Gabel,et al.  Proliferation and activation of vascular endothelial cells in epiretinal membranes from patients with proliferative diabetic retinopathy. An immunohistochemistry and clinical study. , 1994, German journal of ophthalmology.

[72]  M. Spitznas,et al.  Increased lipid peroxide level and myeloperoxidase activity in the vitreous of patients suffering from proliferative vitreoretinopathy , 1993, Graefe's Archive for Clinical and Experimental Ophthalmology.

[73]  Max Costa,et al.  Molecular Responses to Hypoxia-Inducible Factor 1α and Beyond , 2014, Molecular Pharmacology.

[74]  G. A. Limb,et al.  Vascular adhesion molecules in vitreous from eyes with proliferative diabetic retinopathy. , 1999, Investigative ophthalmology & visual science.

[75]  Yoshinori Mitamura,et al.  Vitreous levels of placenta growth factor and vascular endothelial growth factor in patients with proliferative diabetic retinopathy. , 2002, Diabetes care.

[76]  Sergio Romagnani,et al.  An Alternatively Spliced Variant of CXCR3 Mediates the Inhibition of Endothelial Cell Growth Induced by IP-10, Mig, and I-TAC, and Acts as Functional Receptor for Platelet Factor 4 , 2003, The Journal of experimental medicine.

[77]  W. Jiang,et al.  Hepatocyte growth factor regulation: An integral part of why wounds become chronic , 2007, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[78]  G. Brown,et al.  Basic fibroblast growth factor levels in the vitreous of patients with proliferative diabetic retinopathy. , 1990, Archives of ophthalmology.

[79]  Doron Lancet,et al.  MalaCards: an integrated compendium for diseases and their annotation , 2013, Database J. Biol. Databases Curation.

[80]  A. Ljubimov,et al.  Altered expression of growth factors and cytokines in keratoconus, bullous keratopathy and diabetic human corneas. , 2001, Experimental eye research.

[81]  Lei Chen,et al.  Identification of Age-Related Macular Degeneration Related Genes by Applying Shortest Path Algorithm in Protein-Protein Interaction Network , 2013, BioMed research international.

[82]  Edda Klipp,et al.  Biochemical network-based drug-target prediction. , 2010, Current opinion in biotechnology.

[83]  David Maberley,et al.  Expression of integrins in human proliferative diabetic retinopathy membranes. , 2008, Canadian journal of ophthalmology. Journal canadien d'ophtalmologie.

[84]  Aidong Zhang,et al.  HAM-FMD: Mining functional modules in protein-protein interaction networks using ant colony optimization and multi-agent evolution , 2013, Neurocomputing.

[85]  G. Velho,et al.  Sex-specific associations of variants in regulatory regions of NADPH oxidase-2 (CYBB) and glutathione peroxidase 4 (GPX4) genes with kidney disease in type 1 diabetes , 2013, Free radical research.

[86]  Mikko Nikinmaa,et al.  Oxygen-dependent diseases in the retina: role of hypoxia-inducible factors. , 2006, Experimental eye research.

[87]  R. P. Stolk,et al.  Retinopathy, Glucose, and Insulin in an Elderly Population: The Rotterdam Study , 1995, Diabetes.

[88]  Chen Chu,et al.  A computational method for the identification of new candidate carcinogenic and non-carcinogenic chemicals. , 2015, Molecular bioSystems.

[89]  J. H. Kim,et al.  Angiopoietin 2 Induces Pericyte Apoptosis via α3β1 Integrin Signaling in Diabetic Retinopathy , 2014, Diabetes.

[90]  Jian Tajbakhsh,et al.  Proteinase and growth factor alterations revealed by gene microarray analysis of human diabetic corneas. , 2005, Investigative ophthalmology & visual science.

[91]  Peng T Khaw,et al.  Matrix metalloproteinases and their natural inhibitors in fibrovascular membranes of proliferative diabetic retinopathy , 2000, The British journal of ophthalmology.

[92]  P. Campochiaro,et al.  Blockade of vascular endothelial cell growth factor receptor signaling is sufficient to completely prevent retinal neovascularization. , 2000, The American journal of pathology.

[93]  Fabian Kiessling,et al.  Chemokine Cxcl9 attenuates liver fibrosis‐associated angiogenesis in mice , 2012, Hepatology.

[94]  J Roliński,et al.  Influence of low dose rIL-2 treatment on endogenous cytokine production, expression of surface IL-2R and the level of soluble IL-2R in patients with minimal residual disease. , 1999, Leukemia & lymphoma.

[95]  I. Zachary,et al.  VASCULAR ENDOTHELIAL GROWTH FACTOR INDUCES PROTEIN KINASE C (PKC)‐DEPENDENT Akt/PKB ACTIVATION AND PHOSPHATIDYLINOSITOL 3′‐KINASE‐MEDIATED PKCδ PHOSPHORYLATION: ROLE OF PKC IN ANGIOGENESIS , 2002, Cell biology international.

[96]  S. Courtneidge,et al.  The interplay between Src family kinases and receptor tyrosine kinases , 2004, Oncogene.

[97]  Ronald P Danis,et al.  Pharmacologic therapy for diabetic retinopathy , 2003, Expert opinion on emerging drugs.

[98]  T. Springer,et al.  The integrin VLA-4 supports tethering and rolling in flow on VCAM-1 , 1995, The Journal of cell biology.

[99]  R. Salcedo,et al.  Role of Chemokines in Angiogenesis: CXCL12/SDF‐1 and CXCR4 Interaction, a Key Regulator of Endothelial Cell Responses , 2003, Microcirculation.

[100]  Ikuo Inoue,et al.  A common polymorphism in the 5'-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. , 2002, Diabetes.

[101]  L. Aiello,et al.  Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[102]  Ling Zhu,et al.  TGF-β-regulated collagen type I accumulation: role of Src-based signals , 2007 .

[103]  K. Geboes,et al.  Chemokines in proliferative diabetic retinopathy and proliferative vitreoretinopathy , 2006 .

[104]  Lloyd Paul Aiello,et al.  Histopathology of neovascular tissue from eyes with proliferative diabetic retinopathy after intravitreal bevacizumab injection. , 2010, American journal of ophthalmology.

[105]  Reinhard Schneider,et al.  OnTheFly: a tool for automated document-based text annotation, data linking and network generation , 2009, Bioinform..

[106]  K. Skorecki,et al.  Hypoxic induction of vascular endothelial growth factor is markedly decreased in diabetic individuals who do not develop retinopathy. , 2000, Diabetes care.

[107]  Q. Zou,et al.  Approaches for Recognizing Disease Genes Based on Network , 2014, BioMed research international.

[108]  R. Simó,et al.  Hepatocyte growth factor in vitreous and serum from patients with proliferative diabetic retinopathy , 2000, The British journal of ophthalmology.

[109]  G. A. Limb,et al.  Soluble TNF receptors in vitreoretinal proliferative disease. , 2001, Investigative ophthalmology & visual science.

[110]  B Kirchhof,et al.  Leukocyte-mediated endothelial cell injury and death in the diabetic retina. , 2001, The American journal of pathology.

[111]  Yan Li,et al.  Inhibition of retinal neovascularization by gene transfer of small interfering RNA targeting HIF‐1α and VEGF , 2009, Journal of cellular physiology.

[112]  V P Gabel,et al.  Expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on proliferating vascular endothelial cells in diabetic epiretinal membranes. , 1994, The British journal of ophthalmology.

[113]  Wei Xiong,et al.  Active learning for protein function prediction in protein-protein interaction networks , 2014, Neurocomputing.

[114]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[115]  Xiangxiang Zeng,et al.  Integrative approaches for predicting microRNA function and prioritizing disease-related microRNA using biological interaction networks , 2016, Briefings Bioinform..

[116]  Y. Ohmoto,et al.  Expression of transforming growth factor (TGF)-α, TGF-β2 and interleukin 8 messenger RNA in postsurgical and cultured lens epithelial cells obtained from patients with senile cataracts , 1999, Graefe's Archive for Clinical and Experimental Ophthalmology.

[117]  E. Froesch,et al.  Insulin-like growth factors. Studies in diabetics with and without retinopathy. , 1983, The New England journal of medicine.

[118]  Thomas A Einhorn,et al.  TNF-α Mediates Diabetes-Enhanced Chondrocyte Apoptosis During Fracture Healing and Stimulates Chondrocyte Apoptosis Through FOXO1 , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[119]  Xiaolong Wang,et al.  repDNA: a Python package to generate various modes of feature vectors for DNA sequences by incorporating user-defined physicochemical properties and sequence-order effects , 2015, Bioinform..

[120]  Thomas A Einhorn,et al.  High levels of tumor necrosis factor-alpha contribute to accelerated loss of cartilage in diabetic fracture healing. , 2009, The American journal of pathology.

[121]  G. A. Limb,et al.  Distribution of TNF alpha and its reactive vascular adhesion molecules in fibrovascular membranes of proliferative diabetic retinopathy. , 1996, The British journal of ophthalmology.

[122]  Ambuj K. Singh,et al.  Molecular Function Prediction Using Neighborhood Features , 2010, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[123]  Kek Heng Chua,et al.  Investigation of SLC2A1 26177A/G gene polymorphism via high resolution melting curve analysis in Malaysian patients with diabetic retinopathy. , 2012, Journal of diabetes and its complications.

[124]  Brad T. Sherman,et al.  Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources , 2008, Nature Protocols.

[125]  Christian von Mering,et al.  STRING 8—a global view on proteins and their functional interactions in 630 organisms , 2008, Nucleic Acids Res..

[126]  Y. Hui,et al.  Effects of bevacizumab on the neovascular membrane of proliferative diabetic retinopathy: reduction of endothelial cells and expressions of VEGF and HIF-1α , 2012, Molecular vision.

[127]  H P Heidenkummer,et al.  PROLIFERATIVE ACTIVITY IN EPIRETINAL MEMBRANES: The Use of the Monoclonal Antibody Ki-67 in Proliferative Vitreoretinal Diseases , 1992, Retina.

[128]  Ja Seung Koo,et al.  Effect of Intravitreal Bevacizumab on Vascular Endothelial Growth Factor Expression in Patients with Proliferative Diabetic Retinopathy , 2010, Yonsei medical journal.

[129]  Shilling,et al.  Platelet expression of tumour necrosis factor‐alpha (TNF‐α), TNF receptors and intercellular adhesion molecule‐1 (ICAM‐1) in patients with proliferative diabetic retinopathy , 1999, Clinical and experimental immunology.

[130]  P. Reitz,et al.  Effects of diabetes and hypoxia on gene markers of angiogenesis (HGF, cMET, uPA and uPAR, TGF-α, TGF-β, bFGF and Vimentin) in cultured and transplanted rat islets , 2000, Diabetologia.

[131]  E. Gherardi,et al.  Diverse and potent activities of HGF/SF in skin wound repair , 2004, The Journal of pathology.

[132]  R H Watkins,et al.  Retinal vascular endothelial growth factor (VEGF) mRNA expression is altered in relation to neovascularization in oxygen induced retinopathy. , 1996, Current eye research.

[133]  Yi Wang,et al.  Intravitreous vascular endothelial growth factor and hypoxia-inducible factor 1a in patients with proliferative diabetic retinopathy. , 2009, American journal of ophthalmology.

[134]  D. Taub,et al.  Human Interferon-inducible Protein 10 Is a Potent Inhibitor of Angiogenesis in Vivo , 1995 .

[135]  Jing Lu,et al.  A hybrid method for prediction and repositioning of drug Anatomical Therapeutic Chemical classes. , 2014, Molecular bioSystems.

[136]  G. Lizard,et al.  Immunohistochemical analysis of cellular adhesion molecules (ICAM-1, VCAM-1) and VEGF in fibrovascular membranes of patients with proliferative diabetic retinopathy: preliminary study. , 2009, Pathologie-biologie.

[137]  Ling Xia,et al.  Inhibition of Src Kinase Blocks High Glucose–Induced EGFR Transactivation and Collagen Synthesis in Mesangial Cells and Prevents Diabetic Nephropathy in Mice , 2013, Diabetes.

[138]  T. Iwasaki,et al.  CORRELATION OF VASCULAR ENDOTHELIAL GROWTH FACTOR WITH CHEMOKINES IN THE VITREOUS IN DIABETIC RETINOPATHY , 2010, Retina.

[139]  Giorgio Valentini,et al.  Large Scale Ranking and Repositioning of Drugs with Respect to DrugBank Therapeutic Categories , 2012, ISBRA.

[140]  Cristina Hernández,et al.  Free insulin growth factor-I and vascular endothelial growth factor in the vitreous fluid of patients with proliferative diabetic retinopathy. , 2002, American journal of ophthalmology.

[141]  S. H. Wilson,et al.  The therapeutic problem of proliferative diabetic retinopathy: targeting somatostatin receptors. , 2001, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[142]  Kyung Hee Hong,et al.  Monocyte chemoattractant protein-1-induced angiogenesis is mediated by vascular endothelial growth factor-A. , 2005, Blood.

[143]  Yalan Wu,et al.  Anti-VEGF effects of intravitreal erythropoietin in early diabetic retinopathy. , 2010, Frontiers in bioscience.

[144]  Armen B. Shanafelt,et al.  The Functional Role of the ELR Motif in CXC Chemokine-mediated Angiogenesis (*) , 1995, The Journal of Biological Chemistry.

[145]  Sabine Neuss,et al.  Functional Expression of HGF and HGF Receptor/c‐met in Adult Human Mesenchymal Stem Cells Suggests a Role in Cell Mobilization, Tissue Repair, and Wound Healing , 2004, Stem cells.

[146]  L. Aiello,et al.  Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. , 1994, The New England journal of medicine.