{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:10:37Z","timestamp":1788534637575,"version":"build-2803163510"},"reference-count":56,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T00:00:00Z","timestamp":1674432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004569","name":"Ministry of Science and Higher Education","doi-asserted-by":"publisher","award":["4562\/E-290\/M\/2018"],"award-info":[{"award-number":["4562\/E-290\/M\/2018"]}],"id":[{"id":"10.13039\/501100004569","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Accumulating data suggest an important role of growth factors in autoimmune diseases and parasitic nematode infections. Nematodes are used in clinical studies of autoimmune diseases and parasite-derived molecules are widely studied for their therapeutic potential in various types of disorders. However, the effect of nematode infection on growth factors in autoimmune disorders has not been studied. The objective of this study was to evaluate the influence of infection with the intestinal nematode Heligmosomoides polygyrus in murine autoimmune models on the production of growth factors. Here, the level of a variety of growth factors related mainly to angiogenesis was evaluated by protein array in the intestinal mucosa of C57BL\/6 dextran sodium sulfate-induced colitic mice and in cerebral spinal fluid of experimental autoimmune encephalomyelitis (EAE) mice infected with nematodes. In addition, vessel formation was evaluated in the brains of EAE mice infected with H. polygyrus. A significant influence of nematode infection on the level of angiogenic factors was observed. Parasitic infection of colitic mice resulted in upregulation of mucosal AREG, EGF, FGF-2, and IGFBP-3 in the intestine of the host and better adaptation (infectivity). In EAE mice, infection increased the level of FGF-2 and FGF-7 in CSF. In addition, remodeling of brain vessels was observed, with a higher density of long vessels. Nematode-derived factors are promising tools to fight autoimmune diseases and to study angiogenesis.<\/jats:p>","DOI":"10.3390\/life13020321","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T05:46:11Z","timestamp":1674452771000},"page":"321","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Nematode-Induced Growth Factors Related to Angiogenesis in Autoimmune Disease Attenuation"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6595-6228","authenticated-orcid":false,"given":"Marta","family":"Maruszewska-Cheruiyot","sequence":"first","affiliation":[{"name":"Laboratory of Parasitology, General Karol Kaczkowski Military Institute of Hygiene and Epidemiology, 01-163 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Krawczak-W\u00f3jcik","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitology, General Karol Kaczkowski Military Institute of Hygiene and Epidemiology, 01-163 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martyna","family":"Michniowska","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Institute of Functional Biology and Ecology, Faculty of Biology, University of Warsaw, 02-096 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5054-1348","authenticated-orcid":false,"given":"Michael James","family":"Stear","sequence":"additional","affiliation":[{"name":"Department of Animal, Plant and Soil Science, Agribio, La Trobe University, Bundoora 3086, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Machci\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunotherapy, Faculty of Medicine, Lazarski University, 02-662 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3175-4564","authenticated-orcid":false,"given":"Maria","family":"Doligalska","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Institute of Functional Biology and Ecology, Faculty of Biology, University of Warsaw, 02-096 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4924-800X","authenticated-orcid":false,"given":"Katarzyna","family":"Donskow-\u0141ysoniewska","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitology, General Karol Kaczkowski Military Institute of Hygiene and Epidemiology, 01-163 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"674343","DOI":"10.3389\/fimmu.2021.674343","article-title":"Association of circulating vascular endothelial growth factor levels with Autoimmune diseases: A systematic review and meta-analysis","volume":"27","author":"Zhan","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nature10144","article-title":"Molecular mechanisms and clinical applications of angiogenesis","volume":"473","author":"Carmeliet","year":"2011","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/nrm2183","article-title":"Molecular regulation of angiogenesis and lymphangiogenesis","volume":"8","author":"Adams","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1097\/BCR.0b013e3181c7ed82","article-title":"Molecular mediators of angiogenesis","volume":"31","author":"Ucuzian","year":"2010","journal-title":"J. Burn. Care Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.pt.2019.04.009","article-title":"Helminth Therapy\u2014From the Parasite Perspective","volume":"35","author":"Parker","year":"2019","journal-title":"Trends Parasitol."},{"key":"ref_6","first-page":"1","article-title":"Helminth Therapy: Advances in the use of Parasitic Worms Against Inflammatory Bowel Diseases and its Challenges","volume":"27","author":"Doligalska","year":"2018","journal-title":"Helminthologia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1017\/S0031182021001670","article-title":"Use of helminth therapy for management of ulcerative colitis and Crohn\u2019s disease: A systematic review","volume":"149","author":"Shields","year":"2022","journal-title":"Parasitology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.ijpara.2012.10.025","article-title":"Helminth therapy and multiple sclerosis","volume":"43","author":"Fleming","year":"2013","journal-title":"Int. J. Parasitol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.12688\/f1000research.15596.1","article-title":"Helminth parasites and immune regulation","volume":"7","author":"Nutman","year":"2018","journal-title":"F1000Research"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1017\/S0031182010001642","article-title":"Angiogenesis and parasitic helminth-associated neovascularization","volume":"138","author":"Dennis","year":"2011","journal-title":"Parasitology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1016\/S1473-3099(14)70771-6","article-title":"Helminth therapy or elimination: Epidemiological, immunological, and clinical considerations","volume":"14","author":"Wammes","year":"2014","journal-title":"Lancet Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103879","DOI":"10.1016\/j.dci.2020.103879","article-title":"Immunomodulatory potential of nematodes against dendritic cells is dependent on intestinal inflammation","volume":"115","author":"Krawczak","year":"2021","journal-title":"Dev. Comp. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.exppara.2012.07.009","article-title":"Heligmosomoides polygyrus: EAE remission is correlated with different systemic cytokine profiles provoked by L4 and adult nematodes","volume":"132","author":"Krawczak","year":"2012","journal-title":"Exp. Parasitol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1111\/pim.12003","article-title":"Heligmosmoides polygyrus fourth stages induce protection against DSS-induced colitis and change opioid expression in the intestine","volume":"34","author":"Majewski","year":"2012","journal-title":"Parasite Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"G1328","DOI":"10.1152\/ajpgi.00467.2004","article-title":"Acute colitis induced by dextran sulfate sodium progresses to chronicity in C57BL\/6 but not in BALB\/c mice: Correlation between symptoms and inflammation","volume":"288","author":"Melgar","year":"2005","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Donskow-\u0141ysoniewska, K., Bien, J., Brodaczewska, K., Krawczak, K., and Doligalska, M. (2013). Colitis promotes adaptation of an intestinal nematode: A Heligmosomoides polygyrus mouse model system. PLoS ONE, 22.","DOI":"10.1371\/journal.pone.0078034"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0092-8674(91)90638-F","article-title":"Growth factors in development, transformation, and tumorigenesis","volume":"25","author":"Cross","year":"1991","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1152\/physrev.2003.83.3.835","article-title":"Regulation of wound healing by growth factors and cytokines","volume":"83","author":"Werner","year":"2003","journal-title":"Physiol. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.smim.2014.06.003","article-title":"Host protective roles of type 2 immunity: Parasite killing and tissue repair, flip sides of the same coin","volume":"26","author":"Allen","year":"2014","journal-title":"Semin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Maruszewska-Cheruiyot, M., Stear, M.J., Machci\u0144ska, M., and Donskow-\u0141ysoniewska, K. (2022). Importance of TGF\u03b2 in Cancer and Nematode Infection and Their Interaction-Opinion. Biomolecules, 26.","DOI":"10.3390\/biom12111572"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1111\/j.1365-3024.2006.00845.x","article-title":"The role of TGF-beta in mice infected with Heligmosomoides polygyrus","volume":"28","author":"Doligalska","year":"2006","journal-title":"Parasite Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.molbiopara.2016.06.003","article-title":"Host parasite communications\u2014Messages from helminths for the immune system: Parasite communication and cell-cell interactions","volume":"208","author":"Coakley","year":"2016","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.3389\/fimmu.2018.02128","article-title":"Host-parasite interactions promote disease tolerance to intestinal helminth infection","volume":"9","author":"King","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/ncprheum0647","article-title":"Mechanisms of Disease: Angiogenesis in inflammatory diseases","volume":"3","author":"Szekanecz","year":"2007","journal-title":"Nat. Clin. Pract. Rheumatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s40478-014-0084-z","article-title":"Angiogenesis in multiple sclerosis and experimental autoimmune encephalomyelitis","volume":"2","author":"Girolamo","year":"2014","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_26","first-page":"970890","article-title":"Angiogenesis in Inflammatory Bowel Disease","volume":"2015","author":"Alkim","year":"2015","journal-title":"Int. J. Inflam."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrrheum.2015.164","article-title":"Targeting of proangiogenic signalling pathways in chronic inflammation","volume":"12","author":"Tas","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1111\/j.1365-3083.2006.01851.x","article-title":"Decreased expression of VEGF-A in rat experimental autoimmune encephalomyelitis and in cerebrospinal fluid mononuclear cells from patients with multiple sclerosis","volume":"64","author":"Tham","year":"2006","journal-title":"Scand. J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"C1148","DOI":"10.1152\/ajpcell.1999.276.5.C1148","article-title":"VEGF increases permeability of the blood-brain barrier via a nitric oxide synthase\/cGMP-dependent pathway","volume":"276","author":"Mayhan","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.1172\/JCI60842","article-title":"Astrocyte-derived VEGF-A drives blood\u2013brain barrier disruption in CNS inflammatory disease","volume":"122","author":"Argaw","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4618","DOI":"10.4049\/jimmunol.172.7.4618","article-title":"Angiogenesis-inflammation cross-talk: Vascular endothelial growth factor is secreted by activated T cells and induces Th1 polarization","volume":"172","author":"Quintana","year":"2004","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1053\/j.gastro.2008.09.064","article-title":"VEGF-A links angiogenesis and inflammation in inflammatory bowel disease pathogenesis","volume":"136","author":"Scaldaferri","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1086\/340416","article-title":"Soluble egg antigens from Schistosoma mansoni induce angiogenesis-related processes by up-regulating vascular endothelial growth factor in human endothelial cells","volume":"185","author":"Loeffler","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"209","DOI":"10.2307\/3284472","article-title":"Trichinella spiralis: Vascular endothelial growth factor is up-regulated within the nurse cell during the early phase of its formation","volume":"84","author":"Despommier","year":"1998","journal-title":"J. Parasitol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1096\/fj.05-4147com","article-title":"The C. elegans pvf-1 gene encodes a PDGF\/VEGF-like factor able to bind mammalian VEGF receptors and to induce angiogenesis","volume":"20","author":"Tarsitano","year":"2006","journal-title":"FASEB J."},{"key":"ref_36","first-page":"2554","article-title":"ZD1839 (Iressa) induces antiangiogenic effects through inhibition of epidermal growth factor receptor tyrosine kinase","volume":"62","author":"Hirata","year":"2002","journal-title":"Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.immuni.2015.01.020","article-title":"Emerging functions of amphiregulin in orchestrating immunity, inflammation, and tissue repair","volume":"42","author":"Zaiss","year":"2015","journal-title":"Immunity"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1126\/science.1133715","article-title":"Amphiregulin, a TH2 cytokine enhancing resistance to nematodes","volume":"15","author":"Zaiss","year":"2006","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.immuni.2017.09.013","article-title":"Epidermal Growth Factor Receptor Expression Licenses Type-2 Helper T Cells to Function in a T Cell Receptor-Independent Fashion","volume":"17","author":"Minutti","year":"2017","journal-title":"Immunity"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.immuni.2012.09.023","article-title":"Amphiregulin Enhances Regulatory T Cell-Suppressive Function via the Epidermal Growth Factor Receptor","volume":"38","author":"Zaiss","year":"2013","journal-title":"Immunity"},{"key":"ref_41","first-page":"e13084","article-title":"Toxoplasma gondii induces prolonged host epidermal growth factor receptor signalling to prevent parasite elimination by autophagy: Perspectives for in vivo control of the parasite","volume":"21","author":"Mantilla","year":"2019","journal-title":"Cell. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/dvdy.21388","article-title":"Functional evolutionary history of the mouse Fgf gene family","volume":"237","author":"Itoh","year":"2008","journal-title":"Dev. Dyn."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S1357-2725(99)00133-8","article-title":"Fibroblast growth factor-2","volume":"32","author":"Thiery","year":"2000","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3884","DOI":"10.1007\/s12035-021-02367-0","article-title":"Fibroblast Growth Factor Signalling in the Diseased Nervous System","volume":"58","author":"Klimaschewski","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.immuni.2015.06.024","article-title":"Growth Factor FGF2 Cooperates with Interleukin-17 to Repair Intestinal Epithelial Damage","volume":"15","author":"Song","year":"2015","journal-title":"Immunity"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1023\/A:1026642715764","article-title":"Keratinocyte growth factor ameliorates dextran sodium sulfate colitis in mice","volume":"44","author":"Egger","year":"1999","journal-title":"Dig. Dis. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"F\u00f6rster, S., Koziol, U., Sch\u00e4fer, T., Duvoisin, R., Cailliau, K., Vanderstraete, M., Dissous, C., and Brehm, K. (2019). The role of fibroblast growth factor signalling in Echinococcus multilocularis development and host-parasite interaction. PLoS Negl. Trop. Dis., 8.","DOI":"10.1101\/457168"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.immuni.2004.10.011","article-title":"GM-CSF induces expression of soluble VEGF receptor-1 from human monocytes and inhibits angiogenesis in mice","volume":"21","author":"Eubank","year":"2004","journal-title":"Immunity"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.3389\/fimmu.2019.01265","article-title":"Roles of GM-CSF in the Pathogenesis of Autoimmune Diseases: An Update","volume":"4","author":"Lotfi","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/icb.2011.69","article-title":"Protection against Nippostrongylus brasiliensis infection in mice is independent of GM-CSF","volume":"90","author":"Shim","year":"2012","journal-title":"Immunol. Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/S0002-9440(10)64058-8","article-title":"Hepatocyte growth factor enhances vascular endothelial growth factor-induced angiogenesis in vitro and in vivo","volume":"158","author":"Xin","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_52","first-page":"286","article-title":"Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3): Unraveling the Role in Mediating IGF-Independent Effects Within the Cell","volume":"5","author":"Bhardwaj","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e110","DOI":"10.3346\/jkms.2018.33.e110","article-title":"Up-regulation of IGF Binding Protein-3 Inhibits Colonic Inflammatory Response","volume":"26","author":"Kim","year":"2018","journal-title":"J. Korean Med. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/jgh.13461","article-title":"A phenotype of IGFBP-3 knockout mice revealed by dextran sulfate-induced colitis","volume":"32","author":"Yancu","year":"2017","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1620\/tjem.195.21","article-title":"Platelet-derived growth factor and its receptors are expressed in areas of both active inflammation and active fibrosis in inflammatory bowel disease","volume":"195","author":"Kumagai","year":"2001","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s12974-018-1150-4","article-title":"Platelet-derived growth factor predicts prolonged relapse-free period in multiple sclerosis","volume":"15","author":"Iezzi","year":"2018","journal-title":"J. Neuroinflam."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/2\/321\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:14:06Z","timestamp":1760120046000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/2\/321"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,23]]},"references-count":56,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["life13020321"],"URL":"https:\/\/doi.org\/10.3390\/life13020321","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,23]]}}}