{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:17:18Z","timestamp":1788308238515,"version":"build-2803163510"},"reference-count":98,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T00:00:00Z","timestamp":1761350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background. DM frequently causes ESRD, a situation in which survival is impossible without chronic dialysis. This research aimed to study the tissue-regenerative capacity of ESRD patients with\/without DM. For this purpose, two growth factors were studied: NT-3 and VEGF\u03b2. To our knowledge, this is the first study on the serum behavior of NT-3 in patients with ESRD + DM and, very likely, in patients with ESRD alone. VEGF\u03b2 is also very little studied in these patient categories. Since the quasi-permanent inflammation was already clearly proven, this study focused on the anti-inflammatory capacity, taking IL-10 as a prototype, and also the interrelationships between these three factors. Method. All the aforementioned compounds were determined from serum samples, utilizing ELISA kits. Results. The results were surprising, proving a marked polarization of their serum behavior. Although the mean serum levels of NT-3 and VEGF\u03b2 were significantly increased in patients with ESRD + DM compared to those with ESRD alone, most patients in both groups had serum levels below the detection limits of the kits used. Conclusions. Although this research is in its early stages, it generates important conclusions and directions for further research, as the functional connections between the studied parameters are not fully understood.<\/jats:p>","DOI":"10.3390\/jcm14217585","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T09:16:24Z","timestamp":1761729384000},"page":"7585","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Serum Behavior of NT-3 and VEGF\u03b2, Two Unstudied Growth Factors in Patients with Diabetes Mellitus and End-Stage Renal Disease"],"prefix":"10.3390","volume":"14","author":[{"given":"Mihaela","family":"Gheorghiu","sequence":"first","affiliation":[{"name":"Pathophysiology and Immunology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Florina","family":"Trandafir","sequence":"additional","affiliation":[{"name":"Pathophysiology and Immunology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5674-3810","authenticated-orcid":false,"given":"Octavian","family":"Savu","sequence":"additional","affiliation":[{"name":"\u201cN.C. Paulescu\u201d National Institute of Diabetes, Nutrition and Metabolic Diseases, 011233 Bucharest, Romania"},{"name":"Doctoral School, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Pasarica","sequence":"additional","affiliation":[{"name":"Pathophysiology and Immunology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9031-338X","authenticated-orcid":false,"given":"Coralia","family":"Bleotu","sequence":"additional","affiliation":[{"name":"\u201cStefan S. Nicolau\u201d Institute of Virology, 030304 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.4103\/1735-1995.172845","article-title":"Diabetes mellitus and renal failure: Prevention and management","volume":"20","author":"Nasri","year":"2015","journal-title":"J. Res. Med. Sci."},{"key":"ref_2","first-page":"97","article-title":"AT2R-1332 G: A polymorphism and diabetic nephropathy in type 2 diabetes mellitus patients","volume":"2","author":"Rahimi","year":"2013","journal-title":"J. Ren. Inj. Prev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"65","DOI":"10.5812\/nephropathol.7447","article-title":"Are acquired cystic kidney disease and autosomal dominant polycystic kidney disease risk factors for renal cell carcinoma in kidney transplant patients?","volume":"1","author":"Einollahi","year":"2012","journal-title":"J. Nephropathol."},{"key":"ref_4","unstructured":"Pavkov, M.E., and Miyamoto, Y. (2025, September 23). IDF Diabetes Atlas Reports: Diabetes and Kidney Disease. Available online: https:\/\/diabetesatlas.org\/atlas\/diabetes-and-kidney-disease\/."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1001\/jama.2011.861","article-title":"Temporal trends in the prevalence of diabetic kidney disease in the United States","volume":"305","author":"Rue","year":"2011","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"982","DOI":"10.2337\/dc19-1803","article-title":"Incidence and Associations of Chronic Kidney Disease in Community Participants with Diabetes: A 5-Year Prospective Analysis of the EXTEND45 Study","volume":"43","author":"Sukkar","year":"2020","journal-title":"Diabetes Care"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wen, H., Yang, D., Xie, C., Shi, F., Liu, Y., Zhang, J., and Yu, C. (2022). Comparison of trend in chronic kidney disease burden between China, Japan, the United Kingdom, and the United States. Front. Public Health, 10.","DOI":"10.3389\/fpubh.2022.999848"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Jha, R., Lopez-Trevino, S., Kankanamalage, H.R., and Jha, J.C. (2024). Diabetes and Renal Complications: An Overview on Pathophysiology, Biomarkers and Therapeutic Interventions. Biomedicines, 12.","DOI":"10.3390\/biomedicines12051098"},{"key":"ref_9","unstructured":"Agarwal, R. (2025, September 23). Pathogenesis of Diabetic Nephropathy, Chronic Kidney Disease and Type 2 Diabetes, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK571720\/."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1055\/s-0037-1613678","article-title":"AGE-RAGE Stress, Stressors, and Antistressors in Health and Disease","volume":"27","author":"Prasad","year":"2018","journal-title":"Int. J. Angiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1055\/s-0042-1756175","article-title":"Involvement of AGE and Its Receptors in the Pathogenesis of Hypertension in Elderly People and Its Treatment","volume":"31","author":"Prasad","year":"2022","journal-title":"Int. J. Angiol."},{"key":"ref_12","first-page":"1059","article-title":"Signaling pathways in diabetic nephropathy","volume":"31","author":"Kawanami","year":"2016","journal-title":"Histol. Histopathol."},{"key":"ref_13","unstructured":"Srikanth, K.K., and Orrick, J.A. (2025, September 23). Biochemistry, Polyol or Sorbitol Pathways, StatPearls, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK576381\/."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4706","DOI":"10.1016\/S0021-9258(19)67706-9","article-title":"Discovery of a metabolic pathway mediating glucose-induced desensitization of the glucose transport system. Role of hexosamine biosynthesis in the induction of insulin resistance","volume":"266","author":"Marshall","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1096\/fasebj.5.15.1743436","article-title":"New insights into the nutrient metabolic regulation of insulin action and insulin resistance: Role of glucose and amino acids","volume":"5","author":"Marshall","year":"1991","journal-title":"FASEB J."},{"key":"ref_16","first-page":"889","article-title":"Immunohistochemical localization of extracellular matrix components in human diabetic glomerular lesions","volume":"139","author":"Nerlich","year":"1991","journal-title":"Am. J. Pathol."},{"key":"ref_17","first-page":"1381","article-title":"Differential expression of basement membrane collagen in membranous nephropathy","volume":"139","author":"Kim","year":"1991","journal-title":"Am. J. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"31","DOI":"10.2337\/diacare.39.1.31","article-title":"Occurrence of type VI collagen in extracellular matrix of renal glomeruli and its increase in diabetes","volume":"39","author":"Mohan","year":"1990","journal-title":"Diabetes"},{"key":"ref_19","first-page":"484","article-title":"Increased glomerular \u03b11 (IV) expression and deposition in long-term diabetic rats is prevented by chronic glycosaminoglycan treatment","volume":"74","author":"Ceol","year":"1996","journal-title":"Lab. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/S0272-6386(12)80440-9","article-title":"The extracellular matrix in diabetic nephropathy","volume":"22","author":"Ziyadeh","year":"1993","journal-title":"Am. J. Kidney Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.2337\/diab.41.12.1520","article-title":"ECM gene expression and its modulation by insulin in diabetic rats","volume":"41","author":"Fukui","year":"1992","journal-title":"Diabetes"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1111\/imm.12510","article-title":"Protein kinase C in the immune system: From signalling to chromatin regulation","volume":"146","author":"Lim","year":"2015","journal-title":"Immunology"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kazanietz, M.G., and Cooke, M. (2024). Protein kinase C signaling \u201cin\u201d and \u201cto\u201d the nucleus: Master kinases in transcriptional regulation. J. Biol. Chem., 300.","DOI":"10.1016\/j.jbc.2024.105692"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00726-006-0326-x","article-title":"Primary kidney growth and its consequences at the onset of diabetes mellitus","volume":"31","author":"Satriano","year":"2006","journal-title":"Amino Acids"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1093\/eurheartj\/ehv728","article-title":"Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: Results of the EMPA-REG OUTCOME\u00ae trial","volume":"37","author":"Fitchett","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1172\/JCI72271","article-title":"Molecular mechanisms of diabetic kidney disease","volume":"124","author":"Reidy","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Russell McEvoy, M.G., Wells, N.B., Kiley, E.M., Shogan, H., and Fraser, M.G. (2025). Skeletal muscle microvascular hemodynamic responses during hyperinsulinemic-euglycemic clamp in a Zucker Diabetic Sprague Dawley rat model of type 2 diabetes. Front. Physiol., 16.","DOI":"10.3389\/fphys.2025.1568145"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Trandafir, M.F., Savu, O., Pasarica, D., Bleotu, C., and Gheorghiu, M. (2024). Interleukin-6 as a Director of Immunological Events and Tissue Regenerative Capacity in Hemodialyzed Diabetes Patients. Med. Sci., 12.","DOI":"10.3390\/medsci12020031"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wen, Y., Yan, H.R., Wang, B., and Liu, B.C. (2021). Macrophage Heterogeneity in Kidney Injury and Fibrosis. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.681748"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Zhu, Q., He, J., Cao, Y., Liu, X., Nie, W., Han, F., Shi, P., and Shen, X.Z. (2022). Analysis of mononuclear phagocytes disclosed the establishment processes of two macrophage subsets in the adult murine kidney. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.805420"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.kisu.2021.11.006","article-title":"The role of mineralocorticoid receptor activation in kidney inflammation and fibrosis","volume":"12","author":"Luther","year":"2022","journal-title":"Kidney Int. Suppl."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s40828-022-00163-4","article-title":"Macrophages: Shapes and functions","volume":"8","author":"Lendeckel","year":"2022","journal-title":"ChemTexts"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.kint.2018.10.041","article-title":"M2 Macrophages in Kidney Disease Biology, Therapies, and Perspectives","volume":"95","author":"Chen","year":"2019","journal-title":"Kidney Int."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wu, Y.S., Liang, S., Li, D.Y., Wen, J.H., Tang, J.X., and Liu, H.F. (2021). Cell Cycle Dysregulation and Renal Fibrosis. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.714320"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.krcp.2011.12.005","article-title":"The insulin-like growth factor system in chronic kidney disease: Pathophysiology and therapeutic opportunities","volume":"31","author":"Youngman","year":"2012","journal-title":"Kidney Res. Clin. Pract."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8205","DOI":"10.12998\/wjcc.v10.i23.8205","article-title":"Role of serum \u03b22-microglobulin, glycosylated hemoglobin, and vascular endothelial growth factor levels in diabetic nephropathy","volume":"10","author":"Yang","year":"2022","journal-title":"World J. Clin. Cases"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.2337\/dc07-2469","article-title":"Plasma connective tissue growth factor is an independent predictor of end-stage renal disease and mortality in type 1 diabetic nephropathy","volume":"31","author":"Nguyen","year":"2008","journal-title":"Diabetes Care"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1111\/j.1440-1681.2011.05487.x","article-title":"Chronic Kidney Disease Growth Factors in Renal Fibrosis","volume":"38","author":"Boor","year":"2011","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/nrneph.2010.120","article-title":"Renal Fibrosis: Novel Insights into Mechanisms and Therapeutic Targets","volume":"6","author":"Boor","year":"2010","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_40","unstructured":"(2025, September 23). Available online: https:\/\/legislatie.just.ro\/Public\/DetaliiDocument\/274779."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3390\/pathophysiology30020010","article-title":"Neurotrophin-3 (NT-3) as a Potential Biomarker of the Peripheral Nervous System Damage Following Breast Cancer Treatment","volume":"30","author":"Tonyan","year":"2023","journal-title":"Pathophysiology"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Gheorghiu, M., Trandafir, M.-F., Savu, O., Pasarica, D., and Bleotu, C. (2025). Unexpectedly High and Difficult-to-Explain Regenerative Capacity in an 82-Year-Old Patient with Insulin-Requiring Type 2 Diabetes and End-Stage Renal Disease. J. Clin. Med., 14.","DOI":"10.3390\/jcm14082556"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.mcn.2017.04.011","article-title":"Delineating neurotrophin-3 dependent signaling pathways underlying sympathetic axon growth along intermediate targets","volume":"82","author":"Keeler","year":"2017","journal-title":"Mol. Cell Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/bs.vh.2020.04.008","article-title":"Chapter Four\u2014Neurotrophin-3 modulates synaptic transmission, Editor(s): Gerald Litwack","volume":"114","year":"2020","journal-title":"Vitam. Horm."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Bov\u00e9, M., Monto, F., Guillem-Llobat, P., Ivorra, M.D., Noguera, M.A., Zambrano, A., Sirerol-Piquer, M.S., Requena, A.C., Garc\u00eda-Alonso, M., and Tejerina, T. (2021). NT3\/TrkC Pathway Modulates the Expression of UCP-1 and Adipocyte Size in Human and Rodent Adipose Tissue. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.630097"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1161\/ATVBAHA.109.205468","article-title":"Neurotrophin-3 is a novel angiogenic factor capable of therapeutic neovascularization in a mouse model of limb ischemia","volume":"30","author":"Cristofaro","year":"2010","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"eadf6696","DOI":"10.1126\/scisignal.adf6696","article-title":"Hepatic stellate cells maintain liver homeostasis through paracrine neurotrophin-3 signaling that induces hepatocyte proliferation","volume":"16","author":"Trinh","year":"2023","journal-title":"Sci. Signal."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Cacialli, P., and Lucini, C. (2022). Analysis of the Expression of Neurotrophins and Their Receptors in Adult Zebrafish Kidney. Vet. Sci., 9.","DOI":"10.3390\/vetsci9060296"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"11279","DOI":"10.1073\/pnas.92.24.11279","article-title":"Neurotrophin 3 rescues neuronal precursors from apoptosis and promotes neuronal differentiation in the embryonic metanephric kidney","volume":"92","author":"Karavanov","year":"1995","journal-title":"Proc. Natl. Acad Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"C1804","DOI":"10.1152\/ajpcell.2001.281.6.C1804","article-title":"Neurotrophin-3 inhibits HCO 3\u2014Absorption via a cAMP-dependent pathway in renal thick ascending limb","volume":"281","author":"Good","year":"2001","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1681\/ASN.2020040424","article-title":"TrkC Is Essential for Nephron Function and Trans-Activates Igf1R Signaling","volume":"32","author":"Lepa","year":"2021","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s41232-017-0048-3","article-title":"Resident fibroblasts in the kidney: A major driver of fibrosis and inflammation","volume":"37","author":"Sato","year":"2017","journal-title":"Inflamm. Regen."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.5498\/wjp.v14.i12.1804","article-title":"Interaction between serum inflammatory cytokines and brain-derived neurotrophic factor in cognitive function among first-episode schizophrenia patients","volume":"14","author":"Cui","year":"2024","journal-title":"World J. Psychiatry."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1161\/01.RES.0000081594.21764.44","article-title":"Vascular endothelial growth factor-B promotes in vivo angiogenesis","volume":"93","author":"Silvestre","year":"2003","journal-title":"Circ. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1046\/j.1440-1681.2002.03773.x","article-title":"Effects of vascular endothelial growth factor (VEGF)A and VEGFB gene transfer on vascular reserve in a conscious rabbit hindlimb ischaemia model","volume":"29","author":"Wright","year":"2002","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1161\/01.RES.0000182631.33638.77","article-title":"Transgenic overexpression of vascular endothelial growth factor-B isoforms by endothelial cells potentiates postnatal vessel growth in vivo and in vitro","volume":"97","author":"Mould","year":"2005","journal-title":"Circ. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1159\/000139132","article-title":"Vascular effects of FGF-2 and VEGF-B in rabbits with bilateral hind limb ischemia","volume":"46","author":"Wafai","year":"2008","journal-title":"J. Vasc. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s00441-016-2377-y","article-title":"Expression of vascular endothelial growth factor (VEGF)-B and its receptor (VEGFR1) in murine heart, lung and kidney","volume":"365","author":"Muhl","year":"2016","journal-title":"Cell Tissue Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"11709","DOI":"10.1073\/pnas.95.20.11709","article-title":"Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells","volume":"95","author":"Olofsson","year":"1998","journal-title":"Proc. Natl. Acad Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"re1","DOI":"10.1126\/scisignal.259re1","article-title":"Positive and negative modulation of angiogenesis by VEGFR1 ligands","volume":"2","author":"Cao","year":"2009","journal-title":"Sci. Signal."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.cell.2012.08.037","article-title":"Soluble FLT1 Binds Lipid Microdomains in Podocytes to Control Cell Morphology and Glomerular Barrier Function","volume":"151","author":"Jin","year":"2012","journal-title":"Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1161\/ATVBAHA.107.158725","article-title":"Reevaluation of the role of VEGF-B suggests a restricted role in the revascularization of the ischemic myocardium","volume":"28","author":"Li","year":"2008","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1161\/ATVBAHA.108.170878","article-title":"VEGF-B taken to our hearts: Specific effect of VEGF-B in myocardial ischemia","volume":"28","year":"2008","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1161\/CIRCULATIONAHA.108.816454","article-title":"Vascular endothelial growth factor-B induces myocardium-specific angiogenesis and arteriogenesis via vascular endothelial growth factor receptor-1- and neuropilin receptor-1-dependent mechanisms","volume":"119","author":"Rosenlew","year":"2009","journal-title":"Circulation"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"322","DOI":"10.4161\/cam.3.4.9459","article-title":"VEGF-B: A survival, or an angiogenic factor?","volume":"3","author":"Li","year":"2009","journal-title":"Cell Adhes. Migr."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3109\/08977190109001075","article-title":"Isoform-specific expression of VEGF-B in normal tissues and tumors","volume":"19","author":"Li","year":"2001","journal-title":"Growth Factors"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/S1357-2725(01)00027-9","article-title":"Novel VEGF family members: VEGF-B, VEGF-C and VEGF-D","volume":"33","author":"Li","year":"2001","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1097\/01.WCB.0000134477.38980.38","article-title":"Increased severity of cerebral ischemic injury in vascular endothelial growth factor-B-deficient mice","volume":"24","author":"Sun","year":"2004","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"10451","DOI":"10.1523\/JNEUROSCI.1092-08.2008","article-title":"Novel role for vascular endothelial growth factor (VEGF) receptor-1 and its Ligand VEGF-B in motor neuron degeneration","volume":"28","author":"Poesen","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Wei, Y., Han, S., Zhou, R., Xu, P., Zhou, L., Zhu, Z., Kan, Y., Yang, X., Xiang, Y., and Cao, Y. (2022). Increased Serum VEGF-B Level Is Associated with Renal Function Impairment in Patients with Type 2 Diabetes. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.862545"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Gaydarski, L., Petrova, K., Angushev, I., Stanchev, S., Iliev, A., Stamenov, N., Kirkov, V., and Landzhov, B. (2025). Exploring the Molecular Modalities in the Pathogenesis of Diabetic Kidney Disease with a Focus on the Potential Therapeutic Implications. Biomedicines, 13.","DOI":"10.3390\/biomedicines13010050"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41420-023-01304-5","article-title":"Simultaneous blockade of VEGF-B and IL-17A ameliorated diabetic kidney disease by reducing ectopic lipid deposition and alleviating inflammation response","volume":"9","author":"Cao","year":"2023","journal-title":"Cell Death Discov."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/s41392-023-01539-9","article-title":"VEGF-B prevents excessive angiogenesis by inhibiting FGF2\/FGFR1 pathway","volume":"8","author":"Lee","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.imbio.2010.05.025","article-title":"IL-10 regulation of macrophage VEGF production is dependent on macrophage polarisation and hypoxia","volume":"215","author":"Wu","year":"2010","journal-title":"Immunobiology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"108917","DOI":"10.1016\/j.intimp.2022.108917","article-title":"The role of IL-10 in kidney disease","volume":"108","author":"Wei","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1016\/j.jaci.2008.02.026","article-title":"The extended IL-10 superfamily: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29","volume":"121","author":"Commins","year":"2008","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/labinvest.2013.64","article-title":"Interleukin-10 deficiency aggravates kidney inflammation and fibrosis in the unilateral ureteral obstruction mouse model","volume":"93","author":"Jin","year":"2013","journal-title":"Lab. Investig."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1161\/CIRCRESAHA.119.315829","article-title":"Interleukin-10 Deficiency Alters Endothelial Progenitor Cell-Derived Exosome Reparative Effect on Myocardial Repair via Integrin-Linked Kinase Enrichment","volume":"126","author":"Yue","year":"2020","journal-title":"Circ. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"F384","DOI":"10.1152\/ajprenal.00418.2005","article-title":"Mesangial cells initiate compensatory renal tubular hypertrophy via IL-10-induced TGF-beta secretion: Effect of the immunomodulator AS101 on this process","volume":"291","author":"Sinuani","year":"2006","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_80","first-page":"176","article-title":"\u00dcber den bau des glomerulus der s\u00e4ugerniere. Weitere mittleillungen","volume":"32","author":"Zimmerman","year":"1933","journal-title":"Z. Mikrosk. Anat. Forsch."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1084\/jem.170.6.2081","article-title":"Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones","volume":"170","author":"Fiorentino","year":"1989","journal-title":"J. Exp. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1146\/annurev.immunol.19.1.683","article-title":"Interleukin-10 and the interleukin-10 receptor","volume":"19","author":"Moore","year":"2001","journal-title":"Annu. Rev. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.cytogfr.2010.11.001","article-title":"IL-10 family of cytokines","volume":"21","author":"Sabat","year":"2010","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"91","DOI":"10.5500\/wjt.v3.i4.91","article-title":"Role of IL-10 in the progression of kidney disease","volume":"3","author":"Sinuani","year":"2013","journal-title":"World J. Transplant."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1046\/j.1523-1755.1998.00101.x","article-title":"Regulation of smooth muscle \u03b1-actin expression and hypertrophy in cultured mesangial cells","volume":"54","author":"Haney","year":"1998","journal-title":"Kidney Int."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1046\/j.1523-1755.2002.00514.x","article-title":"Mycophenolic acid antagonizes the activation of cultured human mesangial cells","volume":"62","author":"Dubus","year":"2002","journal-title":"Kidney Int."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1159\/000013466","article-title":"Renal growth factors: Past, present and future","volume":"19","author":"Schena","year":"1999","journal-title":"Am. J. Nephrol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1681\/ASN.2008050549","article-title":"The mesangial cell revisited: No cell is an island","volume":"20","author":"Banas","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1152\/physrev.1989.69.4.1347","article-title":"Physiology of the mesangial cell","volume":"69","author":"Mene","year":"1989","journal-title":"Physiol. Rev."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Thomas, H.Y., and Ford Versypt, A.N. (2022). Pathophysiology of mesangial expansion in diabetic nephropathy: Mesangial structure, glomerular biomechanics, and biochemical signaling and regulation. J. Biol. Eng., 16.","DOI":"10.1186\/s13036-022-00299-4"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.yexcr.2012.02.031","article-title":"The glomerular basement membrane","volume":"318","author":"Miner","year":"2012","journal-title":"Exp. Cell Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1111\/j.1464-5491.1994.tb00276.x","article-title":"Localization of fibril\/microfibril and basement membrane collagens in diabetic glomerulosclerosis in type 2 diabetes","volume":"11","author":"Makino","year":"1994","journal-title":"Diabet. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/BF00310191","article-title":"The structural relationship between mesangial cells and basement membrane of the renal glomerulus","volume":"176","author":"Sakai","year":"1987","journal-title":"Anat. Embryol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1007\/BF00180755","article-title":"The glomerular mesangium: Capillary support function and its failure under experimental conditions","volume":"70","author":"Lemley","year":"1992","journal-title":"Clin. Investig."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1159\/000168186","article-title":"Mesangial cell-glomerular basement membrane connections counteract glomerular capillary and mesangium expansion","volume":"10","author":"Kriz","year":"1990","journal-title":"Am. J. Nephrol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Volinsky, N., and Kholodenko, B.N. (2013). Complexity of receptor tyrosine kinase signal processing. Cold Spring Harb. Perspect. Biol., 5.","DOI":"10.1101\/cshperspect.a009043"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3678","DOI":"10.1172\/JCI37914","article-title":"Adult neural stem cells expressing IL-10 confer potent immunomodulation and remyelination in experimental autoimmune encephalitis","volume":"119","author":"Yang","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/nrneph.2014.93","article-title":"Paradoxical association between serum IL-10 levels and risk of cardiovascular events","volume":"10","author":"Carney","year":"2014","journal-title":"Nat. Rev. Nephrol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/21\/7585\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T09:52:49Z","timestamp":1761731569000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/21\/7585"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,25]]},"references-count":98,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["jcm14217585"],"URL":"https:\/\/doi.org\/10.3390\/jcm14217585","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,25]]}}}