E. Ritz and S. R. Orth, Nephropathy in patients with type 2 diabetes mellitus, N. Engl. J. Med, vol.341, pp.1127-1133, 1999.

M. C. Thomas, M. E. Cooper, and P. Zimmet, Changing epidemiology of type 2 diabetes mellitus and associated chronic kidney disease, Nat. Rev. Nephrol, vol.12, pp.73-81, 2016.

K. Umanath and J. B. Lewis, Update on Diabetic Nephropathy: Core Curriculum, Am. J. Kidney Dis, vol.71, pp.884-895, 2018.

H. Cheng and R. C. Harris, Renal endothelial dysfunction in diabetic nephropathy, Cardiovasc. Hematol. Disord. Drug Targets, vol.14, pp.22-33, 2014.

N. Jourde-chiche, F. Fakhouri, L. Dou, J. Bellien, S. Burtey et al., Endothelium structure and function in kidney health and disease, Nat. Rev. Nephrol, vol.15, pp.87-108, 2019.
URL : https://hal.archives-ouvertes.fr/inserm-02160201

S. C. Satchell and F. Braet, Glomerular endothelial cell fenestrations: An integral component of the glomerular filtration barrier, Am. J. Physiol. Ren. Physiol, vol.296, pp.947-956, 2009.

S. Satchell, The role of the glomerular endothelium in albumin handling, Nat. Rev. Nephrol, vol.9, pp.717-725, 2013.

T. J. Rabelink and D. De-zeeuw, The glycocalyx-Linking albuminuria with renal and cardiovascular disease, Nat. Rev. Nephrol, vol.11, pp.667-676, 2015.

R. E. Gilbert, The endothelium in diabetic nephropathy, Curr. Atheroscler. Rep, vol.16, p.410, 2014.

E. J. Weil, K. V. Lemley, C. C. Mason, B. Yee, L. I. Jones et al., Podocyte detachment and reduced glomerular capillary endothelial fenestration promote kidney disease in type 2 diabetic nephropathy, Kidney Int, vol.82, pp.1010-1017, 2012.

P. Sward and B. Rippe, Acute and sustained actions of hyperglycaemia on endothelial and glomerular barrier permeability, Acta Physiol, vol.204, pp.294-307, 2012.

T. W. Tervaert, A. L. Mooyaart, K. Amann, A. H. Cohen, H. T. Cook et al., Pathologic classification of diabetic nephropathy, J. Am. Soc. Nephrol, vol.21, pp.556-563, 2010.

B. Najafian, C. E. Alpers, and A. B. Fogo, Pathology of human diabetic nephropathy, Contrib. Nephrol, vol.170, pp.36-47, 2011.

T. T. Rajah, A. L. Olson, and P. Grammas, Differential glucose uptake in retina-and brain-derived endothelial cells, Microvasc. Res, vol.62, pp.236-242, 2001.

E. Alpert, A. Gruzman, Y. Riahi, R. Blejter, P. Aharoni et al., Delayed autoregulation of glucose transport in vascular endothelial cells, Diabetologia, vol.48, pp.752-755, 2005.

M. Daroux, G. Prevost, H. Maillard-lefebvre, C. Gaxatte, V. D. D'agati et al., Advanced glycation end-products: Implications for diabetic and non-diabetic nephropathies, Diabetes Metab, vol.36, pp.1-10, 2010.

H. Cheng, H. Wang, X. Fan, P. Paueksakon, and R. C. Harris, Improvement of endothelial nitric oxide synthase activity retards the progression of diabetic nephropathy in db/db mice, Kidney Int, vol.82, pp.1176-1183, 2012.

D. J. Kelly, Y. Zhang, C. Hepper, R. M. Gow, K. Jaworski et al., Protein kinase C beta inhibition attenuates the progression of experimental diabetic nephropathy in the presence of continued hypertension, Diabetes, vol.52, pp.512-518, 2003.

F. Cosentino, M. Eto, P. De-paolis, B. Van-der-loo, M. Bachschmid et al., High glucose causes upregulation of cyclooxygenase-2 and alters prostanoid profile in human endothelial cells: Role of protein kinase C and reactive oxygen species, Circulation, vol.107, pp.1017-1023, 2003.

J. Paeng, J. Park, J. E. Um, B. Y. Nam, H. Y. Kang et al., The locally activated renin-angiotensin system is involved in albumin permeability in glomerular endothelial cells under high glucose conditions, Nephrol. Dial. Transplant, vol.32, pp.61-72, 2017.

K. Ebefors, R. J. Wiener, L. Yu, E. U. Azeloglu, Z. Yi et al., Endothelin receptor-A mediates degradation of the glomerular endothelial surface layer via pathologic crosstalk between activated podocytes and glomerular endothelial cells, Kidney Int, vol.96, pp.957-970, 2019.

A. Singh, V. Friden, I. Dasgupta, R. R. Foster, G. I. Welsh et al., High glucose causes dysfunction of the human glomerular endothelial glycocalyx, Am. J. Physiol. Ren. Physiol, vol.300, pp.40-48, 2011.

J. Van-den-born, A. A. Van-kraats, M. A. Bakker, K. J. Assmann, H. B. Dijkman et al., Reduction of heparan sulphate-associated anionic sites in the glomerular basement membrane of rats with streptozotocin-induced diabetic nephropathy, Diabetologia, vol.38, pp.2100-2108, 1995.

M. J. Van-den-hoven, F. Waanders, A. L. Rops, A. B. Kramer, H. Van-goor et al., Regulation of glomerular heparanase expression by aldosterone, angiotensin II and reactive oxygen species, Nephrol. Dial. Transplant, vol.24, pp.2637-2645, 2009.

X. An, L. Zhang, Q. Yao, L. Li, B. Wang et al., The receptor for advanced glycation endproducts mediates podocyte heparanase expression through NF-?B signaling pathway, Mol. Cell. Endocrinol, vol.470, pp.14-25, 2017.

N. Gil, R. Goldberg, T. Neuman, M. Garsen, E. Zcharia et al., Heparanase is essential for the development of diabetic nephropathy in mice, Diabetes, vol.61, pp.208-216, 2012.

D. K. Packham, R. Wolfe, A. T. Reutens, T. Berl, H. L. Heerspink et al., Sulodexide fails to demonstrate renoprotection in overt type 2 diabetic nephropathy, J. Am. Soc. Nephrol, vol.23, pp.123-130, 2012.

E. J. Lewis, J. B. Lewis, T. Greene, L. G. Hunsicker, T. Berl et al., Sulodexide for kidney protection in type 2 diabetes patients with microalbuminuria: A randomized controlled trial, Am. J. Kidney Dis, vol.58, pp.729-736, 2011.

Z. B. Wang, S. Zhang, Y. Li, R. M. Wang, L. C. Tong et al., LY333531, a PKC? inhibitor, attenuates glomerular endothelial cell apoptosis in the early stage of mouse diabetic nephropathy via down-regulating swiprosin-1, Acta Pharmacol. Sin, vol.38, pp.1009-1023, 2017.

H. Peng, Y. F. Xing, Z. C. Ye, C. M. Li, P. L. Luo et al., High glucose induces activation of the local reninangiotensin system in glomerular endothelial cells, Mol. Med. Rep, vol.9, pp.450-456, 2014.

J. Fu, C. Wei, W. Zhang, D. Schlondorff, J. Wu et al., Gene expression profiles of glomerular endothelial cells support their role in the glomerulopathy of diabetic mice, Kidney Int, vol.94, pp.326-345, 2018.

F. M. Ho, S. H. Liu, C. S. Liau, P. J. Huang, and S. Y. Lin-shiau, High glucose-induced apoptosis in human endothelial cells is mediated by sequential activations of c-Jun NH(2)-terminal kinase and caspase-3, Circulation, vol.101, pp.2618-2624, 2000.

S. Majumder and A. Advani, VEGF and the diabetic kidney: More than too much of a good thing, J. Diabetes Complicat, vol.31, pp.273-279, 2017.

B. Hohenstein, B. Hausknecht, K. Boehmer, R. Riess, R. A. Brekken et al., Local VEGF activity but not VEGF expression is tightly regulated during diabetic nephropathy in man, Kidney Int, vol.69, pp.1654-1661, 2006.

Y. Fan, X. Li, W. Xiao, J. Fu, R. C. Harris et al., BAMBI elimination enhances alternative TGF-? signaling and glomerular dysfunction in diabetic mice, Diabetes, vol.64, pp.2220-2233, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01850503

L. Chen, T. Yang, D. W. Lu, H. Zhao, Y. L. Feng et al., Central role of dysregulation of TGF-?/Smad in CKD progression and potential targets of its treatment, Biomed. Pharmacother, vol.101, pp.670-681, 2018.

B. Sutariya, D. Jhonsa, M. N. Saraf, and . Tgf-?, The connecting link between nephropathy and fibrosis, vol.38, pp.39-49, 2016.

E. M. Zeisberg, S. E. Potenta, H. Sugimoto, M. Zeisberg, and R. Kalluri, Fibroblasts in kidney fibrosis emerge via endothelial-to-mesenchymal transition, J. Am. Soc. Nephrol, vol.19, pp.2282-2287, 2008.

J. Li, X. Qu, and J. F. Bertram, Endothelial-myofibroblast transition contributes to the early development of diabetic renal interstitial fibrosis in streptozotocin-induced diabetic mice, Am. J. Pathol, vol.175, pp.1380-1388, 2009.

P. Huynh and Z. Chai, Transforming growth factor beta (TGF?) and related molecules in chronic kidney disease (CKD), Clin. Sci, vol.133, pp.287-313, 2019.

J. Voelker, P. H. Berg, M. Sheetz, K. Duffin, T. Shen et al., Anti-TGF-?1 Antibody Therapy in Patients with Diabetic Nephropathy, J. Am. Soc. Nephrol, vol.28, pp.953-962, 2017.

J. C. Jha, C. Banal, B. S. Chow, M. E. Cooper, and K. Jandeleit-dahm, Diabetes and Kidney Disease: Role of Oxidative Stress, Antioxid. Redox Signal, vol.25, pp.657-684, 2016.

S. Prabhakar, J. Starnes, S. Shi, B. Lonis, and R. Tran, Diabetic nephropathy is associated with oxidative stress and decreased renal nitric oxide production, J. Am. Soc. Nephrol, vol.18, pp.2945-2952, 2007.

E. A. Jaimes, P. Hua, R. X. Tian, and L. Raij, Human glomerular endothelium: Interplay among glucose, free fatty acids, angiotensin II, and oxidative stress, Am. J. Physiol. Ren. Physiol, vol.298, pp.125-132, 2010.

K. Hanai, T. Babazono, I. Nyumura, K. Toya, N. Tanaka et al., Asymmetric dimethylarginine is closely associated with the development and progression of nephropathy in patients with type 2 diabetes, Nephrol. Dial. Transplant, vol.24, pp.1884-1888, 2009.

R. Komers, W. E. Schutzer, J. F. Reed, J. N. Lindsley, T. T. Oyama et al., Altered endothelial nitric oxide synthase targeting and conformation and caveolin-1 expression in the diabetic kidney, Diabetes, vol.55, pp.1651-1659, 2006.

H. You, T. Gao, T. K. Cooper, S. M. Morris, . Jr et al., Diabetic nephropathy is resistant to oral l-arginine or l-citrulline supplementation, Am. J. Physiol. Ren. Physiol, vol.307, pp.1292-1301, 2014.

S. W. Schaffer, C. J. Jong, and M. Mozaffari, Role of oxidative stress in diabetes-mediated vascular dysfunction: Unifying hypothesis of diabetes revisited, Vasc. Pharmacol, vol.57, pp.139-149, 2012.

T. Nishikawa, D. Edelstein, X. L. Du, S. Yamagishi, T. Matsumura et al., Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage, Nature, vol.404, pp.787-790, 2000.

E. Toth, A. Racz, J. Toth, P. M. Kaminski, M. S. Wolin et al., Contribution of polyol pathway to arteriolar dysfunction in hyperglycemia. Role of oxidative stress, reduced NO, and enhanced PGH(2)/TXA(2) mediation, Am. J. Physiol. Heart Circ. Physiol, vol.293, pp.3096-3104, 2007.

M. P. Wautier, O. Chappey, S. Corda, D. M. Stern, A. M. Schmidt et al., Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE, Am. J. Physiol. Endocrinol. Metab, vol.280, pp.685-694, 2001.

A. Kuwabara, M. Satoh, N. Tomita, T. Sasaki, and N. Kashihara, Deterioration of glomerular endothelial surface layer induced by oxidative stress is implicated in altered permeability of macromolecules in Zucker fatty rats, Diabetologia, vol.53, pp.2056-2065, 2010.

H. Qi, G. Casalena, S. Shi, L. Yu, K. Ebefors et al., Glomerular Endothelial Mitochondrial Dysfunction Is Essential and Characteristic of Diabetic Kidney Disease Susceptibility, vol.66, pp.763-778, 2017.

S. Kiritoshi, T. Nishikawa, K. Sonoda, D. Kukidome, T. Senokuchi et al., Reactive oxygen species from mitochondria induce cyclooxygenase-2 gene expression in human mesangial cells: Potential role in diabetic nephropathy, Diabetes, vol.52, pp.2570-2577, 2003.

H. Ha and H. B. Lee, Reactive oxygen species amplify glucose signalling in renal cells cultured under high glucose and in diabetic kidney, Nephrology, vol.10, pp.7-10, 2005.

N. Jourde-chiche, L. Dou, C. Cerini, F. Dignat-george, and P. Brunet, Vascular incompetence in dialysis patients-Protein-bound uremic toxins and endothelial dysfunction, Semin. Dial, vol.24, pp.327-337, 2011.
URL : https://hal.archives-ouvertes.fr/hal-01610435

F. C. Barouch, K. Miyamoto, J. R. Allport, K. Fujita, S. E. Bursell et al., Integrin-mediated neutrophil adhesion and retinal leukostasis in diabetes, Investig. Ophthalmol. Vis. Sci, vol.41, pp.1153-1158, 2000.

R. J. Medina, C. L. Barber, F. Sabatier, F. Dignat-george, J. M. Melero-martin et al., Endothelial Progenitors: A Consensus Statement on Nomenclature. Stem Cells Transl. Med, vol.6, pp.1316-1320, 2017.

J. Wils, J. Favre, and J. Bellien, Modulating putative endothelial progenitor cells for the treatment of endothelial dysfunction and cardiovascular complications in diabetes, Pharmacol. Ther, vol.170, pp.98-115, 2017.

G. P. Fadini, E. Boscaro, S. De-kreutzenberg, C. Agostini, F. Seeger et al., Time course and mechanisms of circulating progenitor cell reduction in the natural history of type 2 diabetes, Diabetes Care, vol.33, pp.1097-1102, 2010.

O. M. Tepper, R. D. Galiano, J. M. Capla, C. Kalka, P. J. Gagne et al., Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures, Circulation, vol.106, pp.2781-2786, 2002.

H. Kang, X. Ma, J. Liu, Y. Fan, and X. Deng, High glucose-induced endothelial progenitor cell dysfunction, Diabetes Vasc. Dis. Res, vol.14, pp.381-394, 2017.

Y. P. Jarajapu, S. Caballero, A. Verma, T. Nakagawa, M. C. Lo et al., Blockade of NADPH oxidase restores vasoreparative function in diabetic CD34+ cells, Investig. Ophthalmol. Vis. Sci, vol.52, pp.5093-5104, 2011.

D. A. Yuen, Y. Zhang, K. Thai, C. Spring, L. Chan et al., Angiogenic dysfunction in bone marrow-derived early outgrowth cells from diabetic animals is attenuated by SIRT1 activation, Stem Cells Transl. Med, vol.1, pp.921-926, 2012.

S. Ueda, S. Yamagishi, T. Matsui, Y. Noda, Y. Jinnouchi et al., Serum levels of advanced glycation end products (AGEs) are inversely associated with the number and migratory activity of circulating endothelial progenitor cells in apparently healthy subjects, Cardiovasc. Ther, vol.30, pp.249-254, 2012.

Q. Chen, L. Dong, L. Wang, L. Kang, and B. Xu, Advanced glycation end products impair function of late endothelial progenitor cells through effects on protein kinase Akt and cyclooxygenase-2, Biochem. Biophys. Res. Commun, vol.381, pp.192-197, 2009.

C. Shen, Q. Li, Y. C. Zhang, G. Ma, Y. Feng et al., Advanced glycation endproducts increase EPC apoptosis and decrease nitric oxide release via MAPK pathways, Biomed. Pharmacother, vol.64, pp.35-43, 2010.

H. Li, X. Zhang, X. Guan, X. Cui, Y. Wang et al., Advanced glycation end products impair the migration, adhesion and secretion potentials of late endothelial progenitor cells, Cardiovasc. Diabetol, vol.11, 2012.

A. D. Bhatwadekar, J. V. Glenn, G. Li, T. M. Curtis, T. A. Gardiner et al., Advanced glycation of fibronectin impairs vascular repair by endothelial progenitor cells: Implications for vasodegeneration in diabetic retinopathy, Investig. Ophthalmol. Vis. Sci, vol.49, pp.1232-1241, 2008.

, Effect of intensive therapy on the development and progression of diabetic nephropathy in the Diabetes Control and Complications Trial. The Diabetes Control and Complications (DCCT) Research Group, Kidney Int, vol.47, pp.1703-1720, 1995.

, DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study Research Group. Intensive Diabetes Treatment and Cardiovascular Outcomes in Type 1 Diabetes: The DCCT/EDIC Study 30-Year Follow-up, Diabetes Control and Complications Trial, vol.39, pp.686-693, 2016.

A. Patel, S. Macmahon, J. Chalmers, B. Neal, L. Billot et al., Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes, N. Engl. J. Med, vol.358, pp.2560-2572, 2008.

S. Ravindran, V. Kuruvilla, K. Wilbur, and S. Munusamy, Nephroprotective Effects of Metformin in Diabetic Nephropathy, J. Cell. Physiol, vol.232, pp.731-742, 2017.

C. R. Triggle and H. Ding, Metformin is not just an antihyperglycaemic drug but also has protective effects on the vascular endothelium, Acta Physiol, vol.219, pp.138-151, 2017.

J. Uribarri and K. R. Tuttle, Advanced glycation end products and nephrotoxicity of high-protein diets, Clin. J. Am. Soc. Nephrol, vol.1, pp.1293-1299, 2006.

R. L. Meek, R. C. Leboeuf, S. A. Saha, C. E. Alpers, K. L. Hudkins et al., Glomerular cell death and inflammation with high-protein diet and diabetes, Nephrol. Dial. Transplant, vol.28, pp.1711-1720, 2013.

N. Bhattacharjee, S. Barma, N. Konwar, S. Dewanjee, and P. Manna, Mechanistic insight of diabetic nephropathy and its pharmacotherapeutic targets: An update, Eur. J. Pharmacol, vol.791, pp.8-24, 2016.

M. P. Schneider, A. Schneider, A. Jumar, I. Kistner, C. Ott et al., Effects of folic acid on renal endothelial function in patients with diabetic nephropathy: Results from a randomized trial, Clin. Sci, vol.127, pp.499-505, 2014.

D. Bolignano, V. Cernaro, G. Gembillo, R. Baggetta, M. Buemi et al., Antioxidant agents for delaying diabetic kidney disease progression: A systematic review and meta-analysis, PLoS ONE, vol.12, 2017.

V. Tsimihodimos, T. D. Filippatos, and M. S. Elisaf, SGLT2 inhibitors and the kidney: Effects and mechanisms, Diabetes Metab. Syndr, vol.12, pp.1117-1123, 2018.

A. Rastogi and A. Bhansali, SGLT2 Inhibitors Through the Windows of EMPA-REG and CANVAS Trials: A Review, vol.8, pp.1245-1251, 2017.

K. W. Mahaffey, M. J. Jardine, S. Bompoint, C. P. Cannon, B. Neal et al., Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups, Circulation, vol.140, pp.739-750, 2019.

D. Z. Khat and M. Husain, Molecular Mechanisms Underlying the Cardiovascular Benefits of SGLT2i and GLP-1RA, Curr. Diabetes Rep, vol.18, p.45, 2018.

F. Shigiyama, N. Kumashiro, M. Miyagi, K. Ikehara, E. Kanda et al., Effectiveness of dapagliflozin on vascular endothelial function and glycemic control in patients with early-stage type 2 diabetes mellitus: DEFENCE study, Cardiovasc. Diabetol, vol.16, 2017.

S. Steven, M. Oelze, A. Hanf, S. Kroller-schon, F. Kashani et al., The SGLT2 inhibitor empagliflozin improves the primary diabetic complications in ZDF rats, Redox Biol, vol.13, pp.370-385, 2017.

Y. Nakatsu, H. Kokubo, B. Bumdelger, M. Yoshizumi, T. Yamamotoya et al., The SGLT2 Inhibitor Luseogliflozin Rapidly Normalizes Aortic mRNA Levels of Inflammation-Related but Not Lipid-Metabolism-Related Genes and Suppresses Atherosclerosis in Diabetic ApoE KO Mice, Int. J. Mol. Sci, vol.18, 1704.

S. Khemais-benkhiat, E. Belcastro, N. Idris-khodja, S. H. Park, L. Amoura et al., Angiotensin II-induced redox-sensitive SGLT1 and 2 expression promotes high glucose-induced endothelial cell senescence, J. Cell. Mol. Med, 2019.
URL : https://hal.archives-ouvertes.fr/hal-02322649

T. Gaspari, I. Spizzo, H. Liu, Y. Hu, R. W. Simpson et al., Dapagliflozin attenuates human vascular endothelial cell activation and induces vasorelaxation: A potential mechanism for inhibition of atherogenesis, Diabetes Vasc. Dis. Res, vol.15, pp.64-73, 2018.

C. Pollock, B. Stefansson, D. Reyner, P. Rossing, C. D. Sjostrom et al., Albuminuria-lowering effect of dapagliflozin alone and in combination with saxagliptin and effect of dapagliflozin and saxagliptin on glycaemic control in patients with type 2 diabetes and chronic kidney disease (DELIGHT): A randomised, double-blind, placebo-controlled trial, Lancet Diabetes Endocrinol, vol.7, pp.429-441, 2019.

S. Shi, S. P. Srivastava, M. Kanasaki, J. He, M. Kitada et al., Interactions of DPP-4 and integrin ?1 influences endothelial-to-mesenchymal transition, Kidney Int, vol.88, pp.479-489, 2015.

N. M. Krasner, Y. Ido, N. B. Ruderman, and J. M. Cacicedo, Glucagon-like peptide-1 (GLP-1) analog liraglutide inhibits endothelial cell inflammation through a calcium and AMPK dependent mechanism, PLoS ONE, vol.9, 2014.

H. Oeseburg, R. A. De-boer, H. Buikema, P. Van-der-harst, W. H. Van-gilst et al., Glucagon-like peptide 1 prevents reactive oxygen species-induced endothelial cell senescence through the activation of protein kinase A, Arterioscler. Thromb. Vasc. Biol, vol.30, pp.1407-1414, 2010.

, This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license, © 2019 by the authors. Licensee MDPI