{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T04:25:34Z","timestamp":1782015934879,"version":"3.54.5"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"content-version":"vor","delay-in-days":185,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002822","name":"Central South University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002822","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>Hypertrophic scar (HTS) is a complicated pathological process induced mainly by burns and wounds, with abnormal proliferation of fibroblasts and the transformation of fibroblasts to myofibroblasts. PAPPA\u2010AS1, a differentially expressed long noncoding RNA (lncRNA) in the HTS tissues, attracted our interests in its potential role and mechanism in the development and process of HTS. In the present study, the regulatory effect of lncRNA PAPPA\u2010AS1 on the Toll\u2010like receptor 4 (TLR4) signal pathway, as well as the molecular mechanism, was investigated. Bioinformatics analysis was utilized to screen the differentially expressed lncRNAs in HTS tissues. PAPPA\u2010AS1 was significantly upregulated in both HTS tissues and hypertrophic scar fibroblast (HTsFb) cells. The expression levels of TLR4, MyD88, TGF\u2010<jats:italic>\u03b2<\/jats:italic>1, collagen I, collagen III, and <jats:italic>\u03b1<\/jats:italic>\u2010SMA were greatly elevated in HTsFb cells. By knocking down PAPPA\u2010AS1, the proliferation of HTsFb cells, TLR4, and TGF\u2010<jats:italic>\u03b2<\/jats:italic>1 signal pathway and the expression of fibrosis markers both in HTsFb cells and HTS tissues were suppressed. It was accompanied by the alleviated pathological state in the HTS tissues, which were significantly reversed by cotransfecting with the pcDNA3.1\u2010TLR4 vector. Positive correlation and interaction were observed between PAPPA\u2010AS1 and TAF15 and between TAF15 and the promoter of TLR4, respectively. In conclusion, lncRNA PAPPA\u2010AS1 might induce the development of HTS by upregulating TLR4 through interacting with TAF15.<\/jats:p>","DOI":"10.1155\/2021\/3170261","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T17:20:15Z","timestamp":1625505615000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["lncRNA PAPPA\u2010AS1 Induces the Development of Hypertrophic Scar by Upregulating TLR4 through Interacting with TAF15"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8922-2392","authenticated-orcid":false,"given":"Pengju","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,5]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.6061\/clinics\/2014(08)11"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.117174"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2018.01.002"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10735-019-09844-w"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.10.030"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-019-0311-8"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28417"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22709"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1159\/000452548"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.11.027"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2018.3430"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2016.02.017"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15973"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2020.5672"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.796631"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.2.558"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejvs.2019.06.018"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1801258"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1663"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.09.007"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22454"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.burns.2012.07.019"},{"key":"e_1_2_10_23_2","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2019.1670508"},{"key":"e_1_2_10_24_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.prs.0000475819.81154.81"},{"key":"e_1_2_10_25_2","doi-asserted-by":"publisher","DOI":"10.3724\/SP.J.1206.2011.00057"},{"key":"e_1_2_10_26_2","article-title":"Gallic acid inhibits LPS induced hypertrophic scar inflammation via Toll-like receptor 4\/nuclear factor-\u03baB\/peroxisome proliferator-ctivated receptor \u03b3 signaling","volume":"11","author":"Pengju Fan S. C.","year":"2018","journal-title":"International Journal of Clinical and Experimental Medicine"},{"key":"e_1_2_10_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-1097-9"},{"key":"e_1_2_10_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-017-0646-x"},{"key":"e_1_2_10_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12381"},{"key":"e_1_2_10_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2018.07.004"},{"key":"e_1_2_10_31_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.33920"},{"key":"e_1_2_10_32_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-018-0259-6"},{"key":"e_1_2_10_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.11.024"},{"key":"e_1_2_10_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.36562"},{"key":"e_1_2_10_35_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8605407"},{"key":"e_1_2_10_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.25873"},{"key":"e_1_2_10_37_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2021.11843"},{"key":"e_1_2_10_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-019-01975-0"},{"key":"e_1_2_10_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.04.036"},{"key":"e_1_2_10_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.06.047"},{"key":"e_1_2_10_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2014.04.020"},{"key":"e_1_2_10_42_2","first-page":"867","article-title":"Dioscin ameliorates peritoneal fibrosis by inhibiting epithelial-to-mesenchymal transition of human peritoneal mesothelial cells via the TLR4\/MyD88\/NF-kappaB signaling pathway","volume":"12","author":"Shao Q.","year":"2019","journal-title":"International Journal of Clinical and Experimental Pathology"},{"key":"e_1_2_10_43_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2006.tb00292.x"},{"key":"e_1_2_10_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0014-5793(01)02656-4"},{"key":"e_1_2_10_45_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M309798200"},{"key":"e_1_2_10_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.5.1280"},{"key":"e_1_2_10_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr201"},{"key":"e_1_2_10_48_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3354"},{"key":"e_1_2_10_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2019.105683"},{"key":"e_1_2_10_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1516-2"}],"container-title":["Mediators of Inflammation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/mi\/2021\/3170261.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/mi\/2021\/3170261.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2021\/3170261","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T09:14:50Z","timestamp":1756372490000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2021\/3170261"}},"subtitle":[],"editor":[{"given":"Yaoyao","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1155\/2021\/3170261"],"URL":"https:\/\/doi.org\/10.1155\/2021\/3170261","archive":["Portico"],"relation":{},"ISSN":["0962-9351","1466-1861"],"issn-type":[{"value":"0962-9351","type":"print"},{"value":"1466-1861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"2021-04-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"3170261"}}