{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T13:55:19Z","timestamp":1781272519541,"version":"3.54.1"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,1,12]],"date-time":"2020-01-12T00:00:00Z","timestamp":1578787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001652","name":"Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg","doi-asserted-by":"publisher","award":["ELAN-17-19-24-M\u00fcller"],"award-info":[{"award-number":["ELAN-17-19-24-M\u00fcller"]}],"id":[{"id":"10.13039\/501100001652","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Forum Allergy Rhinol"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with epithelial expansion and polyp survival. However, the molecular mechanism of this aberrant proliferation is unclear. The purpose of this study was to interrogate derangements of the pappalysin\u2010A\/insulin\u2010like growth factor binding protein\/insulin\u2010like growth factor\u20101 (PAPP\u2010A\/IGFBP\u20104\/5\/IGF\u20101 axis) as a major contributing factor to polyp growth in CRSwNP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Matched tissue and exosomal proteomic arrays including PAPP\u2010A, IGFBP\u20104, IGFBP\u20105, and IGF\u20101 were quantified using aptamer\u2010based methods\/Western blots for proteomic analysis and whole\u2010transcriptome sequencing\/quantitative polymerase chain reaction (qPCR) for transcriptomic analysis in CRSwNP and control patients. Functional PAPP\u2010A assays were then performed in both tissue and exosomes (set 1: n = 20 per group; validation set 2: n = 26 per group).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Tissue and exosomal PAPP\u2010A was significantly overexpressed in CRSwNP compared to controls on both a transcriptomic and proteomic level (<jats:italic>p<\/jats:italic> &lt; 0.0001). Known inhibitors of PAPP\u2010A (stanniocalcin\u20101\/\u20102) were significantly downregulated (<jats:italic>p<\/jats:italic> &lt; 0.0001) as were PAPP\u2010A cleavage products (IGFBP\u20105 <jats:italic>p<\/jats:italic> &lt; 0.0001). PAPP\u2010A function was shown to be increased 5\u2010fold to 6\u2010fold in tissue and exosomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Upregulated tissue and exosomal PAPP\u2010A signaling is significantly associated with CRSwNP and may be an important factor in the promotion of epithelial proliferation and polyp growth. These data lend further support to the emerging concept of exosomal functional and polyomic analyses as a method to study sinonasal pathology.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.22512","type":"journal-article","created":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T05:56:15Z","timestamp":1578894975000},"page":"546-555","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Significant polyomic and functional upregulation of the PAPP\u2010A\/IGFBP\u20104\/5\/IGF\u20101 axis in chronic rhinosinusitis with nasal polyps"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5790-0841","authenticated-orcid":false,"given":"Sarina K.","family":"Mueller","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery Friedrich\u2010Alexander University, Erlangen\u2010N\u00fcrnberg (FAU)  Erlangen Germany"},{"name":"Department of Otolaryngology, Massachusetts Eye and Ear Infirmary Harvard Medical School  Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela L.","family":"Nocera","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Massachusetts Eye and Ear Infirmary Harvard Medical School  Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Workman","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Massachusetts Eye and Ear Infirmary Harvard Medical School  Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Towia","family":"Libermann","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center (BIDMC) Genomics, Proteomics, Bioinformatics and Systems Biology Center, Division of Interdisciplinary Medicine and Biotechnology, BIDMC Harvard Medical School  Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon T.","family":"Dillon","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center (BIDMC) Genomics, Proteomics, Bioinformatics and Systems Biology Center, Division of Interdisciplinary Medicine and Biotechnology, BIDMC Harvard Medical School  Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Stegmann","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery Friedrich\u2010Alexander University, Erlangen\u2010N\u00fcrnberg (FAU)  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Wurm","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery Friedrich\u2010Alexander University, Erlangen\u2010N\u00fcrnberg (FAU)  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinrich","family":"Iro","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery Friedrich\u2010Alexander University, Erlangen\u2010N\u00fcrnberg (FAU)  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Wendler","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery Friedrich\u2010Alexander University, Erlangen\u2010N\u00fcrnberg (FAU)  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0783-8861","authenticated-orcid":false,"given":"Benjamin S.","family":"Bleier","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Massachusetts Eye and Ear Infirmary Harvard Medical School  Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.26249"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22189"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22226"},{"key":"e_1_2_6_5_1","volume-title":"PAPPA pappalysin 1 [Homo sapiens (human)]. 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