{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T03:46:05Z","timestamp":1778557565357,"version":"3.51.4"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1F1A1067185"],"award-info":[{"award-number":["2020R1F1A1067185"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Endometriosis is a gynecological disease prevalent in women of reproductive age, and it is characterized by the ectopic presence and growth of the eutopic endometrium. The pathophysiology and diagnostic biomarkers of endometriosis have not yet been comprehensively determined. To discover molecular markers and pathways underlying the pathogenesis of endometriosis, we identified differentially expressed genes (DEGs) in three Gene Expression Omnibus microarray datasets (GSE11691, GSE23339, and GSE7305) and performed gene set enrichment analysis (GSEA) and protein\u2013protein interaction (PPI) network analyses. We also validated the identified genes <jats:italic>via<\/jats:italic> immunohistochemical analysis of tissues obtained from patients with endometriosis or healthy volunteers. A total of 118 DEGs (79 upregulated and 39 downregulated) were detected in each dataset with a lower (fold change) FC cutoff (log2|FC| &amp;gt; 1), and 17 DEGs (11 upregulated and six downregulated) with a higher FC cutoff (log2|FC| &amp;gt; 2). KEGG and GO functional analyses revealed enrichment of signaling pathways associated with inflammation, complement activation, cell adhesion, and extracellular matrix in endometriotic tissues. Upregulation of seven genes (<jats:italic>C7<\/jats:italic>, <jats:italic>CFH<\/jats:italic>, <jats:italic>FZD7<\/jats:italic>, <jats:italic>LY96<\/jats:italic>, <jats:italic>PDLIM3<\/jats:italic>, <jats:italic>PTGIS<\/jats:italic>, and <jats:italic>WISP2<\/jats:italic>) out of 17 was validated <jats:italic>via<\/jats:italic> comparison with external gene sets, and protein expression of four genes (<jats:italic>LY96<\/jats:italic>, <jats:italic>PDLIM3<\/jats:italic>, <jats:italic>PTGIS<\/jats:italic>, and <jats:italic>WISP2<\/jats:italic>) was further analyzed by immunohistochemistry and western blot analysis. Based on these results, we suggest that TLR4\/NF-\u03baB and Wnt\/frizzled signaling pathways, as well as estrogen receptors, regulate the progression of endometriosis. These pathways may be therapeutic and diagnostic targets for endometriosis.<\/jats:p>","DOI":"10.3389\/fendo.2022.942368","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T06:46:54Z","timestamp":1666248414000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["Identification and analysis of novel endometriosis biomarkers via integrative bioinformatics"],"prefix":"10.3389","volume":"13","author":[{"given":"Sung-Jin","family":"Bae","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunju","family":"Jo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min Kyoung","family":"Cho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung-Sook","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Young","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaewon","family":"Shim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun Hak","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jang-Kyung","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongryeol","family":"Ryu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun Joo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jongkil","family":"Joo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ki-Tae","family":"Ha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00389-5","article-title":"Endometriosis is a chronic systemic disease: Clinical challenges and novel innovations","volume":"397","author":"Taylor","year":"2021","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1007\/s13669-017-0187-1","article-title":"Endometriosis: Epidemiology, diagnosis and clinical management","volume":"6","author":"Parasar","year":"2017","journal-title":"Curr Obstet Gynecol Rep"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222111700","article-title":"Pathogenesis of endometriosis: New insights into prospective therapies","volume":"22","author":"Kapoor","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B4","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s00404-012-2357-8","article-title":"Pathogenesis of endometriosis: The role of genetics, inflammation and oxidative stress","volume":"286","author":"Augoulea","year":"2012","journal-title":"Arch Gynecol Obstet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00389-5","article-title":"Endometriosis is a chronic systemic disease: Clinical challenge and novel innovations","volume":"397","author":"Taylor","year":"2021","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2017.01.009","article-title":"Biomarkers in endometriosis: Challenges and opportunities","volume":"107","author":"Ahn","year":"2017","journal-title":"Fertil Steril"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21051750","article-title":"Biomarkers for the noninvasive diagnosis of endometriosis: State of the art and future perspectives","volume":"21","author":"Anastasiu","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioz016","article-title":"Endometriosis biomarkers: Will codevelopment in academia-industry partnerships result in new and robust noninvasive diagnostic tests","volume":"101","author":"MDH","year":"2019","journal-title":"Biol Reprod"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000001063","article-title":"Current biomarkers for the detection of endometriosis","volume":"133","author":"Tian","year":"2020","journal-title":"Chin Med J (Engl)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1055\/a-1380-3693","article-title":"Diagnosis and treatment of endometriosis. guideline of the dggg, sggg and oeggg (S2k level, awmf registry number 015\/045, august 2020)","volume":"81","author":"Burghaus","year":"2021","journal-title":"Geburtshilfe Frauenheilkd"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2020.144545","article-title":"Endometriosis research in the -omics era","volume":"741","author":"Goulielmos","year":"2020","journal-title":"Gene"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/bs.adgen.2015.11.004","article-title":"Integrative analysis of multi-omics data for discovery and functional studies of complex human diseases","volume":"93","author":"Sun","year":"2016","journal-title":"Adv Genet"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.10171","article-title":"Identification of key genes and pathways in endometriosis by integrated expression profiles analysis","volume":"8","author":"Cui","year":"2020","journal-title":"PeerJ"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2021.1966087","article-title":"Screening differentially expressed genes between endometriosis and ovarian cancer to find new biomarkers for endometriosis","volume":"53","author":"Lu","year":"2021","journal-title":"Ann Med"},{"key":"B15","doi-asserted-by":"publisher","first-page":"8442","DOI":"10.1038\/s41598-020-65606-9","article-title":"Bioinformatic analysis reveals the importance of epithelial-mesenchymal transition in the development of endometriosis","volume":"10","author":"Chen","year":"2020","journal-title":"Sci Rep"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2019.8214","article-title":"Identification of differentially expressed genes and signaling pathways involved in endometriosis by integrated bioinformatics analysis","volume":"19","author":"Dai","year":"2020","journal-title":"Exp Ther Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.071128","article-title":"Endometrial-peritoneal interactions during endometriotic lesion establishment","volume":"173","author":"Hull","year":"2008","journal-title":"Am J Pathol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1210\/me.2010-0371","article-title":"Functional microrna involved in endometriosis","volume":"25","author":"Hawkins","year":"2011","journal-title":"Mol Endocrinol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703451104","article-title":"Human endometriosis is associated with plasma cells and overexpression of b lymphocyte stimulator","volume":"104","author":"Hever","year":"2007","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24358","article-title":"Transcriptional profiling of endometriosis tissues identifies genes related to organogenesis defects","volume":"228","author":"Crispi","year":"2013","journal-title":"J Cell Physiol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm254","article-title":"Geoquery: A bridge between the gene expression omnibus (Geo) and bioconductor","volume":"23","author":"Davis","year":"2007","journal-title":"Bioinformatics"},{"key":"B22","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate - a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J R Stat Soc B"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202106487","article-title":"A microfluidic device to fabricate one-step cell bead-laden hydrogel struts for tissue engineering","volume":"18","author":"Kim","year":"2022","journal-title":"Small"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-9-80","article-title":"The impact of endometrioma and laparoscopic cystectomy on serum anti-mullerian hormone levels","volume":"9","author":"Hwu","year":"2011","journal-title":"Reprod Biol Endocrinol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/s0015-0282(02)03431-3","article-title":"Peritoneal defects and the development of endometriosis in relation to the timing of endoscopic surgery during the menstrual cycle","volume":"78","author":"Schweppe","year":"2002","journal-title":"Fertil Steril"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2689","article-title":"Dgidb: Mining the druggable genome","volume":"10","author":"Griffith","year":"2013","journal-title":"Nat Methods"},{"key":"B27","article-title":"Inactivation of prostaglandin h synthase and prostacyclin synthase by phenylbutazone. requirement for peroxidative metabolism","volume":"27","author":"Reed","year":"1985","journal-title":"Mol Pharmacol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.109.077370","article-title":"Defining postpartum uterine disease and the mechanisms of infection and immunity in the female reproductive tract in cattle","volume":"81","author":"Sheldon","year":"2009","journal-title":"Biol Reprod"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-14-1338","article-title":"Complement pathway is frequently altered in endometriosis and endometriosis-associated ovarian cancer","volume":"20","author":"Suryawanshi","year":"2014","journal-title":"Clin Cancer Res"},{"key":"B30","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.fertnstert.2012.04.047","article-title":"The ferroimmunomodulatory role of ectopic endometriotic stromal cells in ovarian endometriosis","volume":"98","author":"Kobayashi","year":"2012","journal-title":"Fertil Steril"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1177\/1933719117704905","article-title":"Endometrial stromal and epithelial cells exhibit unique aberrant molecular defects in patients with endometriosis","volume":"25","author":"Logan","year":"2018","journal-title":"Reprod Sci"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19082385","article-title":"Chronic niche inflammation in endometriosis-associated infertility: Current understanding and future therapeutic strategies","volume":"19","author":"Lin","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B33","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1146\/annurev-pathmechdis-012419-032654","article-title":"The origin and pathogenesis of endometriosis","volume":"15","author":"Wang","year":"2020","journal-title":"Annu Rev Pathol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s12958-018-0391-5","article-title":"A novel and compact review on the role of oxidative stress in female reproduction","volume":"16","author":"Lu","year":"2018","journal-title":"Reprod Biol Endocrinol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00935","article-title":"Regulation of inflammation pathways and inflammasome by sex steroid hormones in endometriosis","volume":"10","author":"Garcia-Gomez","year":"2019","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dez019","article-title":"Estrogen receptor beta upregulates Ccl2 Via nf-kappab signaling in endometriotic stromal cells and recruits macrophages to promote the pathogenesis of endometriosis","volume":"34","author":"Gou","year":"2019","journal-title":"Hum Reprod"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1210\/en.2019-00442","article-title":"Genomic function of estrogen receptor beta in endometriosis","volume":"160","author":"Han","year":"2019","journal-title":"Endocrinology"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.745548","article-title":"Pathogenesis based diagnosis and treatment of endometriosis","volume":"12","author":"Koninckx","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B39","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1530\/REP-17-0092","article-title":"High-throughput mrna sequencing of stromal cells from endometriomas and endometrium","volume":"154","author":"Rekker","year":"2017","journal-title":"Reproduction"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.8730","article-title":"Common and specific gene signatures among three different endometriosis subtypes","volume":"8","author":"Jiang","year":"2020","journal-title":"Peerj"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0241","article-title":"Evidence for the presence of toll-like receptor 4 system in the human endometrium","volume":"90","author":"Hirata","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.2194","article-title":"Effect of eritoran, an antagonist of Md2-Tlr4, on mortality in patients with severe sepsis: The access randomized trial","volume":"309","author":"Opal","year":"2013","journal-title":"JAMA"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2008.01.006","article-title":"Lps\/Tlr4 signal transduction pathway","volume":"42","author":"Lu","year":"2008","journal-title":"Cytokine"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2009.05.006","article-title":"Seong SY. partial role of Tlr4 as a receptor responding to damage-associated molecular pattern","volume":"125","author":"Lee","year":"2009","journal-title":"Immunol Lett"},{"key":"B45","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/s41392-020-00443-w","article-title":"Metabolism pathways of arachidonic acids: Mechanisms and potential therapeutic targets","volume":"6","author":"Wang","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2011.00024","article-title":"Prostacyclin: An inflammatory paradox","volume":"2","author":"Stitham","year":"2011","journal-title":"Front Pharmacol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203239","article-title":"Activators and target genes of Rel\/Nf-kappab transcription factors","volume":"18","author":"Pahl","year":"1999","journal-title":"Oncogene"},{"key":"B48","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1016\/j.bbrc.2009.09.028","article-title":"Cyclic stretch induces cyclooxygenase-2 gene expression in vascular endothelial cells Via activation of nuclear factor kappa-beta","volume":"389","author":"Zhao","year":"2009","journal-title":"Biochem Biophys Res Commun"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.054775","article-title":"Protection against cytokine toxicity through endoplasmic reticulum and mitochondrial stress prevention by prostacyclin synthase overexpression in insulin-producing cells","volume":"285","author":"Gurgul-Convey","year":"2010","journal-title":"J Biol Chem"},{"key":"B50","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.tem.2005.05.008","article-title":"Estrogen stimulation of cox-2-Derived Pgi2 confers atheroprotection","volume":"16","author":"Shah","year":"2005","journal-title":"Trends Endocrinol Metab"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dep421","article-title":"An additive interaction between the nfkappab and estrogen receptor signalling pathways in human endometrial epithelial cells","volume":"25","author":"King","year":"2010","journal-title":"Hum Reprod"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(81)90033-8","article-title":"Peritoneal fluid thromboxane B2 and 6-Keto-Prostaglandin F1 alpha in endometriosis","volume":"140","author":"Drake","year":"1981","journal-title":"Am J Obstet Gynecol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/s0002-9378(85)80221-0","article-title":"Prostacyclin and thromboxane in gynecology and obstetrics","volume":"152","author":"Ylikorkala","year":"1985","journal-title":"Am J Obstet Gynecol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2010.02.008","article-title":"DNA Microarray analysis in a mouse model for endometriosis and validation of candidate factors with human adenomyosis","volume":"85","author":"Kusakabe","year":"2010","journal-title":"J Reprod Immunol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1021\/pr500384n","article-title":"Ovarian endometriosis signatures established through discovery and directed mass spectrometry analysis","volume":"13","author":"Vehmas","year":"2014","journal-title":"J Proteome Res"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.145","article-title":"Fzd7 has a critical role in cell proliferation in triple negative breast cancer","volume":"30","author":"Yang","year":"2011","journal-title":"Oncogene"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1186\/2045-3701-2-14","article-title":"Wnt signaling in development and disease","volume":"2","author":"Yang","year":"2012","journal-title":"Cell Biosci"},{"key":"B58","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1007\/s12672-021-00429-2","article-title":"Cancer chemoprevention through frizzled receptors and emt","volume":"12","author":"Sompel","year":"2021","journal-title":"Discovery Oncol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M602308200","article-title":"Wnt\/Beta-catenin signaling is a normal physiological response to mechanical loading in bone","volume":"281","author":"Robinson","year":"2006","journal-title":"J Biol Chem"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2024502118","article-title":"Reduced levels of prostaglandin I2 synthase: A distinctive feature of the cancer-free trichothiodystrophy","volume":"118","author":"Lombardi","year":"2021","journal-title":"Proc Natl Acad Sci USA"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1615\/ForumImmunDisTher.v1.i3","article-title":"Cross-regulation between wnt and nf-kappab signaling pathways","volume":"1","author":"Du","year":"2010","journal-title":"For Immunopathol Dis Therap"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00378","article-title":"Crosstalk between Wnt\/Beta-catenin and nf-kappab signaling pathway during inflammation","volume":"7","author":"Ma","year":"2016","journal-title":"Front Immunol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/87920","article-title":"Adult mice deficient in actinin-associated lim-domain protein reveal a developmental pathway for right ventricular cardiomyopathy","volume":"7","author":"Pashmforoush","year":"2001","journal-title":"Nat Med"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01316-10","article-title":"Ccn5, a novel transcriptional repressor of the transforming growth factor beta signaling pathway","volume":"31","author":"Sabbah","year":"2011","journal-title":"Mol Cell Biol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-010-0098-7","article-title":"Ccn5: Biology and pathophysiology","volume":"4","author":"Russo","year":"2010","journal-title":"J Cell Commun Signal"},{"key":"B66","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.yjmcc.2010.04.010","article-title":"The opposing effects of Ccn2 and Ccn5 on the development of cardiac hypertrophy and fibrosis","volume":"49","author":"Yoon","year":"2010","journal-title":"J Mol Cell Cardiol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01335-07","article-title":"Role of wisp-2\/Ccn5 in the maintenance of a differentiated and noninvasive phenotype in human breast cancer cells","volume":"28","author":"Fritah","year":"2008","journal-title":"Mol Cell Biol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.511964","article-title":"The novel secreted adipokine Wnt1-inducible signaling pathway protein 2 (Wisp2) is a mesenchymal cell activator of canonical wnt","volume":"289","author":"Grunberg","year":"2014","journal-title":"J Biol Chem"},{"key":"B69","doi-asserted-by":"publisher","first-page":"5383","DOI":"10.1038\/ncomms6383","article-title":"The oestrogen receptor alpha-regulated lncrna Neat1 is a critical modulator of prostate cancer","volume":"5","author":"Chakravarty","year":"2014","journal-title":"Nat Commun"},{"key":"B70","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.theriogenology.2016.08.028","article-title":"Endometrial prostaglandin synthases, ovarian steroids, and oxytocin receptors in mares with oxytocin-induced luteal maintenance","volume":"87","author":"Rebordao","year":"2017","journal-title":"Theriogenology"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00018.2003","article-title":"17beta-estradiol decreases vascular tone in cerebral arteries by shifting cox-dependent vasoconstriction to vasodilation","volume":"285","author":"Ospina","year":"2003","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B72","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s10549-020-05817-w","article-title":"Phase ib clinical trial of the anti-frizzled antibody vantictumab (Omp-18r5) plus paclitaxel in patients with locally advanced or metastatic Her2-negative breast cancer","volume":"184","author":"Diamond","year":"2020","journal-title":"Breast Cancer Res Treat"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1120068109","article-title":"Wnt pathway inhibition Via the targeting of frizzled receptors results in decreased growth and tumorigenicity of human tumors","volume":"109","author":"Gurney","year":"2012","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-018-0035-2","article-title":"A selective peptide inhibitor of frizzled 7 receptors disrupts intestinal stem cells","volume":"14","author":"Nile","year":"2018","journal-title":"Nat Chem Biol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.20665","article-title":"Discovery of novel frizzled-7 inhibitors by targeting the receptor's transmembrane domain","volume":"8","author":"Zhang","year":"2017","journal-title":"Oncotarget"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2011.558190","article-title":"Eritoran tetrasodium (E5564) treatment for sepsis: Review of preclinical and clinical studies","volume":"7","author":"Barochia","year":"2011","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1039\/c8fo01445k","article-title":"Isofraxidin targets the Tlr4\/Md-2 axis to prevent osteoarthritis development","volume":"9","author":"Jin","year":"2018","journal-title":"Food Funct"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.115.222570","article-title":"Curcumin analog L48h37 prevents lipopolysaccharide-induced Tlr4 signaling pathway activation and sepsis Via targeting Md2","volume":"353","author":"Wang","year":"2015","journal-title":"J Pharmacol Exp Ther"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1038\/srep25130","article-title":"Discovery of new Md2 inhibitor from chalcone derivatives with anti-inflammatory effects in lps-induced acute lung injury","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci Rep"},{"key":"B80","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s40656-018-0191-4","article-title":"Phenylbutazone (Bute, pbz, epz): One drug across two species","volume":"40","author":"Worboys","year":"2018","journal-title":"Hist Philos Life Sci"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1159\/000439172","article-title":"Pharmacogenetic effect of complement factor h gene polymorphism in response to the initial intravitreal injection of bevacizumab for wet age-related macular degeneration","volume":"54","author":"Medina","year":"2015","journal-title":"Ophthalmic Res"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2012.05.040","article-title":"Cumulative effect of risk alleles in cfh, Arms2, and vegfa on the response to ranibizumab treatment in age-related macular degeneration","volume":"119","author":"Smailhodzic","year":"2012","journal-title":"Ophthalmology"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2010.193680","article-title":"Cfh, vegf and Htra1 promoter genotype may influence the response to intravitreal ranibizumab therapy for neovascular age-related macular degeneration","volume":"96","author":"McKibbin","year":"2012","journal-title":"Br J Ophthalmol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.06440616","article-title":"Pathogenic variants in complement genes and risk of atypical hemolytic uremic syndrome relapse after eculizumab discontinuation","volume":"12","author":"Fakhouri","year":"2017","journal-title":"Clin J Am Soc Nephrol"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2009.08.011","article-title":"Maintenance of kidney function following treatment with eculizumab and discontinuation of plasma exchange after a third kidney transplant for atypical hemolytic uremic syndrome associated with a cfh mutation","volume":"55","author":"Davin","year":"2010","journal-title":"Am J Kidney Dis"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.942368\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T06:46:58Z","timestamp":1666248418000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.942368\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,20]]},"references-count":85,"alternative-id":["10.3389\/fendo.2022.942368"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.942368","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,20]]},"article-number":"942368"}}