{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:59:26Z","timestamp":1790139566570,"version":"4.0.1"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T00:00:00Z","timestamp":1502409600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T00:00:00Z","timestamp":1502409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hepatic fibrosis is caused by exaggerated wound healing response to chronic injury, which eventually leads to hepatic cirrhosis. Differentiation of hepatic stellate cells (HSCs) to myofibroblast-like cells by inflammatory cytokines is the critical step in fibrosis. This step is accompanied by enlargement of the endoplasmic reticulum (ER) and Golgi apparatus, suggesting that protein synthesis and secretion are augmented in the activated HSCs. However, the process of rearrangement of secretory organelles and their functions remain to be fully elucidated. Here, we revealed that differentiation alters early secretory gene expression. We observed significant isoform-specific upregulation of the inner coat protein complex II (COPII) components, Sec23A and Sec24D, via the transmembrane bZIP transcription factor, CREB3L2\/BBF2H7, during HSC activation. Moreover, knockdown of these components abrogated the activation, suggesting that Sec23A\/Sec24D-mediated ER to Golgi trafficking is required for HSC activation.<\/jats:p>","DOI":"10.1038\/s41598-017-08703-6","type":"journal-article","created":{"date-parts":[[2017,8,7]],"date-time":"2017-08-07T15:34:53Z","timestamp":1502120093000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["CREB3L2-mediated expression of Sec23A\/Sec24D is involved in hepatic stellate cell activation through ER-Golgi transport"],"prefix":"10.1038","volume":"7","author":[{"given":"Shotaro","family":"Tomoishi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Fukushima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Shinohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Katada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2478-2687","authenticated-orcid":false,"given":"Kota","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,11]]},"reference":[{"key":"8703_CR1","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1002\/hep.25670","volume":"56","author":"DY Zhang","year":"2012","unstructured":"Zhang, D. Y. & Friedman, S. L. Fibrosis-dependent mechanisms of hepatocarcinogenesis. Hepatology \n                           56, 769\u2013775, doi:10.1002\/hep.25670 (2012).","journal-title":"Hepatology"},{"key":"8703_CR2","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1152\/physrev.00013.2007","volume":"88","author":"SL Friedman","year":"2008","unstructured":"Friedman, S. L. Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol. Rev. \n                           88, 125\u2013172, doi:10.1152\/physrev.00013.2007 (2008).","journal-title":"Physiol. Rev."},{"key":"8703_CR3","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004700","volume":"5","author":"SL Friedman","year":"2013","unstructured":"Friedman, S. L., Sheppard, D., Duffield, J. S. & Violette, S. Therapy for fibrotic diseases: nearing the starting line. Sci. Transl. Med. \n                           5, 167sr161, doi:10.1126\/scitranslmed.3004700 (2013).","journal-title":"Sci. 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COPII - a flexible vesicle formation system. Curr. Opin. Cell Biol. 25, 420\u2013427. doi:10.1016\/j.ceb.2013.04.005 (2013).","journal-title":"Curr. Opin. Cell Biol."},{"key":"8703_CR7","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.1128\/MCB.01552-06","volume":"27","author":"S Kondo","year":"2007","unstructured":"Kondo, S. et al. BBF2H7, a novel transmembrane bZIP transcription factor, is a new type of endoplasmic reticulum stress transducer. Mol. Cell. Biol. \n                           27, 1716\u20131729, doi:10.1128\/MCB.01552-06 (2007).","journal-title":"Mol. Cell. Biol."},{"key":"8703_CR8","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201609100","author":"T Ishikawa","year":"2017","unstructured":"Ishikawa, T. et al. UPR transducer BBF2H7 allows export of type II collagen in a cargo- and developmental stage-specific manner. J. Cell Biol. 216, 1761\u20131774. doi:10.1083\/jcb.201609100 (2017).","journal-title":"J. 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Hepatology \n                           65, 983\u2013998, doi:10.1002\/hep.28921 (2017).","journal-title":"Hepatology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-08703-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-08703-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-08703-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T08:28:52Z","timestamp":1671784132000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-08703-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,11]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["8703"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-08703-6","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,11]]},"assertion":[{"value":"29 March 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 August 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"7992"}}