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Meanwhile, we have shown that long pentraxin 3 (PTX3), an essential component of humoral innate immunity that is produced at sites of infection and inflammation, was overproduced in human nasal mucosae and secretions of CRSsNP. Therefore, this study was aimed to investigate how FGF\u20102 regulates PTX3 expression in human CRSsNP nasal mucosa\u2010derived fibroblast cells (hNMDFs). The FGF\u20102 treatment caused <jats:italic>ptx3<\/jats:italic> mRNA expression and PTX3 protein induction and secretion. In parallel, a differential expression of FGF receptor (FGFR)\u22121 to FGFR\u20104 was observed in hNMDFs and human nasal tissues. While conventionally known PI3K\/Akt\/mTOR and AP\u20101 pathways following FGFR activation were shown to be involved, the protein kinase C\u03b4 (PKC\u03b4) and cAMP response element\u2010binding protein (CREB) were also found to be as critical signaling molecules in FGF\u20102\u2010induced PTX3 induction. The PKC\u03b4 and CREB activation could be detected in total cells and in the cell nucleus. Accordingly, a novel CREB binding sequence was detected in the human <jats:italic>ptx3<\/jats:italic> promoter region and could interact with activated CREB in cells challenged with FGF\u20102. Surprisingly, the phospholipase D (PLD), but not phosphoinositide\u2010 and phosphatidylcholine\u2010phospholipase C, was necessarily required for PKC\u03b4 and CREB activation. Therefore, we demonstrated here for the first time that FGF\u20102 mediates PTX3 production not only through PI\u20103K\/Akt\/mTOR and AP\u20101 activation, but also through a novel FGFR\u2013PLD\u2013PKC\u03b4\u2013CREB cellular signaling pathway.<\/jats:p>","DOI":"10.1002\/jcp.30657","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T07:12:01Z","timestamp":1639379521000},"page":"1871-1887","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Novel involvement of PLD\u2013PKC\u03b4\u2013CREB axis in regulating FGF\u20102\u2010mediated pentraxin 3 production in human nasal fibroblast cells"],"prefix":"10.1002","volume":"237","author":[{"given":"Yih\u2010Jeng","family":"Tsai","sequence":"first","affiliation":[{"name":"School of Medicine Fu Jen Catholic University  New Taipei City Taiwan"},{"name":"Department of Otolaryngology Head and Neck Surgery Shin Kong Wu Ho\u2010Su Memorial Hospital Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming\u2010Chieh","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Medicine Fu Jen Catholic University  New Taipei City Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pi\u2010Hui","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine Fu Jen Catholic University  New Taipei City Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9248-5030","authenticated-orcid":false,"given":"Wen\u2010Bin","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine Fu Jen Catholic University  New Taipei City Taiwan"},{"name":"Graduate Institute of Biomedical and Pharmaceutical Science, College of Medicine Fu Jen Catholic University New Taipei City Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,12,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00017.2008"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.13.8172"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.09.003"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-030409-101305"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2004.1464"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.114.009217"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M601023200"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3482"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2007-0028"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000501145"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R115.692020"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2825"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.10.011"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2016.30.4360"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00490.2006"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/920517"},{"key":"e_1_2_8_18_1","first-page":"5925","article-title":"Gold nanoparticles induce heme oxygenase\u20101 expression through Nrf2 activation and Bach1 export in human vascular endothelial cells","volume":"10","author":"Lai T.\u2010H.","year":"2015","journal-title":"International Journal of Nanomedicine"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2016.30.4255"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2014.28.4077"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajr.2006.20.2894"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0608345"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12043"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01287.x"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(88)90258-5"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.09.029"},{"issue":"12","key":"e_1_2_8_27_1","first-page":"4848","article-title":"The angiogenesis inhibitor SU5416 has long\u2010lasting effects on vascular endothelial growth factor receptor phosphorylation and function","volume":"6","author":"Mendel D. 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