{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T08:32:20Z","timestamp":1758097940030,"version":"3.44.0"},"reference-count":51,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T00:00:00Z","timestamp":1722816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic rhinosinusitis without nasal polyp (CRSsNP) is characterized by tissue repair\/remodeling and the subepithelial stroma region in whose nasal mucosa has been reported by us to have thromboxane A<jats:sub>2<\/jats:sub> (TXA<jats:sub>2<\/jats:sub>) prostanoid (TP) receptor and overexpress connective tissue growth factor (CTGF). Therefore, this study aimed to investigate the relationship between TP receptor activation and CTGF production\/function in human CRSsNP nasal mucosa stromal fibroblasts. We found that TP agonists including U46619 and IBOP ([1S\u2010[1\u03b1,2\u03b1(Z),3\u03b2(1E,3\u2009S*),4\u03b1]]\u20107\u2010[3\u2010[3\u2010hydroxy\u20104\u2010(4\u2010iodophenoxy)\u20101\u2010butenyl]\u20107\u2010oxabicyclo[2.2.1]hept\u20102\u2010yl]\u20105\u2010heptenoic acid) could promote CTGF protein\/messenger RNA expression and secretion. The pharmacological intervention and TP activation assay with U46619 identified the possible participation of PKC\u03bc, PKC\u03b4, nuclear factor\u2010\u03baB (NF\u2010\u03baB), and cyclic AMP response element\u2010binding protein (CREB) phosphorylation\/activation in the CTGF induction. Moreover, a phorbol ester\u2014phorbol\u201012\u2010myristate 13\u2010acetate (PMA) exhibited a similar cellular signaling and CTGF production profile to that elicited by TP activation. However, further small interfering RNA interference analysis revealed that only NF\u2010\u03baB and PKC\u03b4\u2010CREB pathways were necessarily required for TP\u2010mediated CTGF production, which could not be completely supported by those findings from PMA. Finally, in a functional assay, although CTGF did not affect fibroblast proliferation, TP\u2010mediated CTGF could drive novel self\u2010migration in fibroblasts both in the scratch\/wound healing and transwell apparatus assays. Meanwhile, the overall staining for stress fibers and formation of the lamellipodia and filopodia\u2010like structures was concomitantly increased in the treated migrating cells. Collectively, we provided here that novel TP mediates CTGF production and self\u2010migration in human nasal fibroblasts through NF\u2010\u03baB and PKC\u03b4\u2010CREB signaling pathways. More importantly, we also demonstrated that thromboxane, TP receptor, CTGF, and stromal fibroblasts may act in concert in the tissue remodeling\/repair process during CRSsNP development and progression.<\/jats:p>","DOI":"10.1002\/jcp.31390","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:34:59Z","timestamp":1722904499000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The novel thromboxane prostanoid receptor mediates CTGF production to drive human nasal fibroblast self\u2010migration through NF\u2010\u03baB and PKC\u03b4\u2010CREB signaling pathways"],"prefix":"10.1002","volume":"239","author":[{"given":"Shih\u2010Lun","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology Chi Mei Medical Center, Yongkang District Tainan Taiwan"},{"name":"Department of Pet Care and Grooming Chung Hwa University of Medical Technology Tainan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yih\u2010Jeng","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Shin Kong Wu Ho\u2010Su Memorial Hospital Taipei Taiwan"},{"name":"School of Medicine Fu Jen Catholic University New Taipei City Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiunn\u2010Min","family":"Shieh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Chi Mei Medical Center Tainan 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 Fu Jen Catholic University New Taipei City Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,8,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-1981(99)00164-X"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb826"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2867-14-61"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.02.036"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11020308"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.591537"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-023-00762-x"},{"issue":"6","key":"e_1_2_9_9_1","first-page":"1359","article-title":"Biological characteristics of CCN proteins in tumor development","volume":"21","author":"Barreto S. 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