{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T23:51:20Z","timestamp":1769039480121,"version":"3.49.0"},"reference-count":74,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Endometriosis is a benign disease affecting one in ten women of reproductive age worldwide. Although the pain level is not correlated to the extent of the disease, it is still one of the cardinal symptoms strongly affecting the patients\u2019 quality of life. Yet, a molecular mechanism of this pathology, including the formation of pain, remains to be defined. Recent studies have indicated a close interaction between newly generated nerve cells and macrophages, leading to neurogenic inflammation in the pelvic area. In this context, the responsiveness of an endometriotic cell culture model was characterized upon inflammatory stimulation by employing a multi-omics approach, including proteomics, metabolomics and eicosanoid analysis. Differential proteomic profiling of the 12-Z endometriotic cell line treated with TNF\u03b1 and IL1\u03b2 unexpectedly showed that the inflammatory stimulation was able to induce a protein signature associated with neuroangiogenesis, specifically including neuropilins (NRP1\/2). Untargeted metabolomic profiling in the same setup further revealed that the endometriotic cells were capable of the autonomous production of 7,8-dihydrobiopterin (BH2), 7,8-dihydroneopterin, normetanephrine and epinephrine. These metabolites are related to the development of neuropathic pain and the former three were found up-regulated upon inflammatory stimulation. Additionally, 12-Z cells were found to secrete the mono-oxygenated oxylipin 16-HETE, a known inhibitor of neutrophil aggregation and adhesion. Thus, inflammatory stimulation of endometriotic 12-Z cells led to specific protein and metabolite expression changes suggesting a direct involvement of these epithelial-like cells in endometriosis pain development.<\/jats:p>","DOI":"10.3390\/biom11081230","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T21:27:40Z","timestamp":1629235660000},"page":"1230","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Epithelial Cell Line Derived from Endometriotic Lesion Mimics Macrophage Nervous Mechanism of Pain Generation on Proteome and Metabolome Levels"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7024-7493","authenticated-orcid":false,"given":"Benjamin","family":"Neuditschko","sequence":"first","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Stra\u00dfe 38, 1090 Vienna, Austria"},{"name":"Department of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Stra\u00dfe 42, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1095-4521","authenticated-orcid":false,"given":"Marlene","family":"Leibetseder","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Stra\u00dfe 38, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7702-3468","authenticated-orcid":false,"given":"Julia","family":"Brunmair","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Stra\u00dfe 38, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6782-4117","authenticated-orcid":false,"given":"Gerhard","family":"Hagn","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Stra\u00dfe 38, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukas","family":"Skos","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Stra\u00dfe 38, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4378-9254","authenticated-orcid":false,"given":"Marlene C.","family":"Gerner","sequence":"additional","affiliation":[{"name":"Division of Biomedical Science, University of Applied Sciences, FH Campus Wien, Favoritenstra\u00dfe 226, 1100 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8930-4574","authenticated-orcid":false,"given":"Samuel M.","family":"Meier-Menches","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Stra\u00dfe 38, 1090 Vienna, Austria"},{"name":"Department of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Stra\u00dfe 42, 1090 Vienna, Austria"},{"name":"Joint Metabolome Facility, Faculty of Chemistry, University of Vienna, Waehringer Stra\u00dfe 38, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1810-4951","authenticated-orcid":false,"given":"Iveta","family":"Yotova","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4964-0642","authenticated-orcid":false,"given":"Christopher","family":"Gerner","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Stra\u00dfe 38, 1090 Vienna, Austria"},{"name":"Joint Metabolome Facility, Faculty of Chemistry, University of Vienna, Waehringer Stra\u00dfe 38, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1067\/j.cpradiol.2011.01.003","article-title":"Beyond the boundaries-endometriosis: Typical and atypical locations","volume":"40","author":"Sonavane","year":"2011","journal-title":"Curr. Probl. Diagn. Radiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"450468","DOI":"10.1155\/2015\/450468","article-title":"Inhibition of adhesion, proliferation, and invasion of primary endometriosis and endometrial stromal and ovarian carcinoma cells by a nonhyaluronan adhesion barrier gel","volume":"2015","author":"Renner","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1093\/humupd\/dmv060","article-title":"Kinase signalling pathways in endometriosis: Potential targets for non-hormonal therapeutics","volume":"22","author":"McKinnon","year":"2016","journal-title":"Hum. Reprod. Update"},{"key":"ref_4","first-page":"12","article-title":"Towards an understanding of the molecular mechanisms of endometriosis-associated symptoms (Review)","volume":"2","author":"Imanaka","year":"2020","journal-title":"World Acad. Sci. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/aogs.12026","article-title":"The rASRM score and the Enzian classification for endometriosis: Their strengths and weaknesses","volume":"92","author":"Haas","year":"2013","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ejogrb.2016.07.497","article-title":"Mechanisms of pain in endometriosis","volume":"209","author":"Morotti","year":"2017","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1093\/humrep\/dep427","article-title":"Nerve fibres in ovarian endometriotic lesions in women with ovarian endometriosis","volume":"25","author":"Zhang","year":"2010","journal-title":"Hum. Reprod."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ejogrb.2014.05.027","article-title":"Prevalence and severity of cyclic leg pain in women with endometriosis and in controls\u2014Effect of laparoscopic surgery","volume":"179","author":"Walch","year":"2014","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/S1074-3804(99)80006-1","article-title":"Correlation between endometriosis and pelvic pain","volume":"6","author":"Porpora","year":"1999","journal-title":"J. Am. Assoc. Gynecol. Laparosc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1111\/j.1751-486X.2008.00362.x","article-title":"Endometriosis and Chronic Pelvic Pain: Unraveling the Mystery Behind this Complex Condition","volume":"12","author":"Bloski","year":"2008","journal-title":"Nurs. Womens Health"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"106","DOI":"10.2174\/1573404813666170306163448","article-title":"Molecular and Cellular Pathogenesis of Endometriosis","volume":"14","author":"Klemmt","year":"2018","journal-title":"Curr. Womens Health Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.3892\/mmr.2017.6783","article-title":"Elevated expression of transient receptor potential vanilloid type 1 in dorsal root ganglia of rats with endometriosis","volume":"16","author":"Lian","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/jog.13559","article-title":"Involvement of immune cells in the pathogenesis of endometriosis","volume":"44","author":"Izumi","year":"2018","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1002\/path.2588","article-title":"Downregulation of CD36 results in reduced phagocytic ability of peritoneal macrophages of women with endometriosis","volume":"219","author":"Chuang","year":"2009","journal-title":"J. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1586\/eci.11.53","article-title":"Immune interactions in endometriosis","volume":"7","author":"Herington","year":"2011","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_16","first-page":"7","article-title":"The role of cell-mediated immunity in pathogenesis of endometriosis","volume":"159","author":"Dmowski","year":"1994","journal-title":"Acta Obstet. Gynecol. Scand. Suppl."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"390","DOI":"10.3343\/alm.2020.40.5.390","article-title":"Cytokines, Angiogenesis, and Extracellular Matrix Degradation are Augmented by Oxidative Stress in Endometriosis","volume":"40","author":"Nanda","year":"2020","journal-title":"Ann. Lab. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s12958-018-0441-z","article-title":"Villainous role of estrogen in macrophage-nerve interaction in endometriosis","volume":"16","author":"Liang","year":"2018","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1016\/j.ajpath.2015.04.012","article-title":"Estradiol is a critical mediator of macrophage-nerve cross talk in peritoneal endometriosis","volume":"185","author":"Greaves","year":"2015","journal-title":"Am. J. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3389\/fimmu.2013.00009","article-title":"Endometriosis, a disease of the macrophage","volume":"4","author":"Capobianco","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4243","DOI":"10.1046\/j.0953-816X.2000.01326.x","article-title":"Vascular endothelial growth factor is a neurotrophic factor which stimulates axonal outgrowth through the flk-1 receptor","volume":"12","author":"Sondell","year":"2000","journal-title":"Eur. J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1080\/09513590.2016.1232789","article-title":"Innovative approach in assessing the role of neurogenesis, angiogenesis, and lymphangiogenesis in the pathogenesis of external genital endometriosis","volume":"32","author":"Sheveleva","year":"2016","journal-title":"Gynecol. Endocrinol."},{"key":"ref_23","first-page":"564","article-title":"The endometrial immune environment of women with endometriosis","volume":"25","author":"Houshdaran","year":"2019","journal-title":"Hum. Reprod. Update"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1177\/1933719108330087","article-title":"Inflammation in reproductive disorders","volume":"16","author":"Weiss","year":"2009","journal-title":"Reprod. Sci."},{"key":"ref_25","first-page":"2513","article-title":"Inflammatory cytokines IL-6, IL-10, IL-13, TNF-alpha and peritoneal fluid flora were associated with infertility in patients with endometriosis","volume":"22","author":"Wang","year":"2018","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.ccr.2013.11.007","article-title":"Impeding macrophage entry into hypoxic tumor areas by Sema3A\/Nrp1 signaling blockade inhibits angiogenesis and restores antitumor immunity","volume":"24","author":"Casazza","year":"2013","journal-title":"Cancer Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s12974-017-0828-3","article-title":"Macrophage and nerve interaction in endometriosis","volume":"14","author":"Wu","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1093\/humupd\/dmu025","article-title":"Central changes associated with chronic pelvic pain and endometriosis","volume":"20","author":"Brawn","year":"2014","journal-title":"Hum. Reprod. Update"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/j.fertnstert.2014.07.1244","article-title":"World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project: II. Clinical and covariate phenotype data collection in endometriosis research","volume":"102","author":"Vitonis","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_30","first-page":"333","article-title":"Expression of transient receptor potentials of vanilloid subtype 1 and pain in endometriosis","volume":"47","author":"Song","year":"2012","journal-title":"Zhonghua Fu Chan Ke Za Zhi"},{"key":"ref_31","first-page":"1033","article-title":"Angiogenesis, lymphangiogenesis and neurogenesis in endometriosis","volume":"5","author":"Peters","year":"2013","journal-title":"Front. Biosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1093\/humupd\/dmu021","article-title":"Peripheral changes in endometriosis-associated pain","volume":"20","author":"Morotti","year":"2014","journal-title":"Hum. Reprod. Update"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12014-019-9235-3","article-title":"Discovery of non-invasive biomarkers for the diagnosis of endometriosis","volume":"16","author":"Irungu","year":"2019","journal-title":"Clin. Proteom."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1177\/1535370220903270","article-title":"Challenges in uncovering non-invasive biomarkers of endometriosis","volume":"245","author":"Hudson","year":"2020","journal-title":"Exp. Biol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"R35","DOI":"10.1530\/RAF-20-0047","article-title":"Metabolomics in endometriosis: Challenges and perspectives for future studies","volume":"2","author":"Ortiz","year":"2021","journal-title":"Reprod. Fertil."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"311","DOI":"10.2174\/156802607779941314","article-title":"Eicosanoids in Inflammation: Biosynthesis, Pharmacology, and Therapeutic Frontiers","volume":"7","author":"Khanapure","year":"2007","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/nature07201","article-title":"Origin and physiological roles of inflammation","volume":"454","author":"Medzhitov","year":"2008","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1016\/S0002-9440(10)63030-1","article-title":"Identification of an invasive, N-cadherin-expressing epithelial cell type in endometriosis using a new cell culture model","volume":"159","author":"Zeitvogel","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"96","DOI":"10.5114\/ceji.2015.50840","article-title":"Pro-inflammatory cytokines for evaluation of inflammatory status in endometriosis","volume":"40","author":"Malutan","year":"2015","journal-title":"Cent. Eur. J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1074\/mcp.RA119.001886","article-title":"The Challenge of Classifying Metastatic Cell Properties by Molecular Profiling Exemplified with Cutaneous Melanoma Cells and Their Cerebral Metastasis from Patient Derived Mouse Xenografts","volume":"19","author":"Neuditschko","year":"2020","journal-title":"Mol. Cell. Proteom."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1002\/pmic.201300553","article-title":"Suspension trapping (STrap) sample preparation method for bottom-up proteomics analysis","volume":"14","author":"Zougman","year":"2014","journal-title":"Proteomics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1074\/mcp.RA117.000425","article-title":"Proteomics and metabolomics identify molecular mechanisms of aging potentially predisposing for chronic lymphocytic leukemia","volume":"17","author":"Mayer","year":"2018","journal-title":"Mol. Cell. Proteom."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1038\/nbt.1511","article-title":"MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification","volume":"26","author":"Cox","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"727","DOI":"10.3389\/fphar.2019.00727","article-title":"Proteome analysis reveals distinct mitochondrial functions linked to interferon response patterns in activated CD4+ and CD8+ T cells","volume":"10","author":"Gerner","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5989","DOI":"10.1021\/pr5008625","article-title":"Comprehensive assessment of proteins regulated by dexamethasone reveals novel effects in primary human peripheral blood mononuclear cells","volume":"13","author":"Bileck","year":"2014","journal-title":"J. Proteome Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/bioinformatics\/btp101","article-title":"ClueGO: A Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks","volume":"25","author":"Bindea","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"D442","DOI":"10.1093\/nar\/gky1106","article-title":"The PRIDE database and related tools and resources in 2019: Improving support for quantification data","volume":"47","author":"Csordas","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"W606","DOI":"10.1093\/nar\/gkm324","article-title":"LIPID MAPS online tools for lipid research","volume":"35","author":"Fahy","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/nri1703","article-title":"NF-kappaB: Linking inflammation and immunity to cancer development and progression","volume":"5","author":"Karin","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.3389\/fimmu.2019.02035","article-title":"Human Monocyte Subsets and Phenotypes in Major Chronic Inflammatory Diseases","volume":"10","author":"Kapellos","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1534\/genetics.114.168211","article-title":"A novel ribosomopathy caused by dysfunction of RPL10 disrupts neurodevelopment and causes X-linked microcephaly in humans","volume":"198","author":"Brooks","year":"2014","journal-title":"Genetics"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/humupd\/dmy001","article-title":"Basic mechanisms of vascularization in endometriosis and their clinical implications","volume":"24","author":"Laschke","year":"2018","journal-title":"Hum. Reprod. Update"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s10456-009-9141-9","article-title":"Cooperation between integrin alphavbeta3 and VEGFR2 in angiogenesis","volume":"12","author":"Somanath","year":"2009","journal-title":"Angiogenesis"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.cbi.2018.12.004","article-title":"Subterminal hydroxyeicosatetraenoic acids: Crucial lipid mediators in normal physiology and disease states","volume":"299","author":"Shoieb","year":"2019","journal-title":"Chem. Biol. Interact."},{"key":"ref_57","first-page":"446","article-title":"A neutrophil-derived cytochrome P450-dependent metabolite of arachidonic acid modulates neutrophil behavior","volume":"128","author":"Kraemer","year":"1987","journal-title":"Am. J. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Liang, Y., Wang, W., Huang, J., Tan, H., Liu, T., Shang, C., Liu, D., Guo, L., and Yao, S. (2015). Potential Role of Semaphorin 3A and Its Receptors in Regulating Aberrant Sympathetic Innervation in Peritoneal and Deep Infiltrating Endometriosis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0146027"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1007\/978-0-387-76715-4_4","article-title":"Role of semaphorins during axon growth and guidance","volume":"621","author":"Koncina","year":"2007","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pneurobio.2017.04.005","article-title":"Optineurin in amyotrophic lateral sclerosis: Multifunctional adaptor protein at the crossroads of different neuroprotective mechanisms","volume":"154","author":"Markovinovic","year":"2017","journal-title":"Prog. Neurobiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.3389\/fphys.2018.01236","article-title":"Semaphorins and Their Receptors: From Axonal Guidance to Atherosclerosis","volume":"9","author":"Hu","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1523\/JNEUROSCI.4445-12.2013","article-title":"Neurogenesis continues in the third trimester of pregnancy and is suppressed by premature birth","volume":"33","author":"Malik","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.biocel.2017.03.017","article-title":"Effect of 7,8-dihydroneopterin mediated CD36 down regulation and oxidant scavenging on oxidised low-density lipoprotein induced cell death in human macrophages","volume":"87","author":"Shchepetkina","year":"2017","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1196\/annals.1351.014","article-title":"Neurogenic inflammation and arthritis","volume":"1069","author":"Levine","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1097\/01.ta.0000196802.91829.cc","article-title":"Norepinephrine modulates the inflammatory and proliferative phases of wound healing","volume":"60","author":"Gosain","year":"2006","journal-title":"J. Trauma"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"63","DOI":"10.4049\/jimmunol.190.Supp.63.7","article-title":"Catecholamines promote an M2 macrophage activation phenotype (P1299)","volume":"190","author":"Grailer","year":"2013","journal-title":"J. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1159\/000358524","article-title":"Induction of M2 regulatory macrophages through the beta2-adrenergic receptor with protection during endotoxemia and acute lung injury","volume":"6","author":"Grailer","year":"2014","journal-title":"J. Innate Immun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"295","DOI":"10.5483\/BMBRep.2015.48.5.008","article-title":"Adrenergic receptor beta2 activation by stress promotes breast cancer progression through macrophages M2 polarization in tumor microenvironment","volume":"48","author":"Qin","year":"2015","journal-title":"BMB Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.pneurobio.2006.08.001","article-title":"Noradrenergic pain modulation","volume":"80","author":"Pertovaara","year":"2006","journal-title":"Prog. Neurobiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/0304-3940(87)90167-4","article-title":"Activation of unmyelinated afferents in chronically lesioned nerves by adrenaline and excitation of sympathetic efferents in the cat","volume":"82","author":"Habler","year":"1987","journal-title":"Neurosci. Lett."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1080\/00016340903176826","article-title":"Endometriosis-associated nerve fibers and pain","volume":"88","author":"Medina","year":"2009","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1146\/annurev.bi.54.070185.003501","article-title":"Biosynthesis and Metabolism of Tetrahydrobiopterin and Molybdopterin","volume":"54","author":"Nichol","year":"1985","journal-title":"Annu. Rev. Biochem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.2174\/138920111798357393","article-title":"GCH1, BH4 and pain","volume":"12","author":"Latremoliere","year":"2011","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1177\/1933719110391279","article-title":"TRPV1 expression on peritoneal endometriosis foci is associated with chronic pelvic pain","volume":"18","author":"Rocha","year":"2011","journal-title":"Reprod. Sci."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/8\/1230\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:45:58Z","timestamp":1760165158000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/8\/1230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,17]]},"references-count":74,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["biom11081230"],"URL":"https:\/\/doi.org\/10.3390\/biom11081230","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,17]]}}}