CREB3L2-mediated expression of Sec23A/Sec24D is involved in hepatic stellate cell activation through ER-Golgi transport

Abstract 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...

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Autores principales: Shotaro Tomoishi, Shinichi Fukushima, Kentaro Shinohara, Toshiaki Katada, Kota Saito
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/962d23b9ba8644049160c4dea9506310
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spelling oai:doaj.org-article:962d23b9ba8644049160c4dea95063102021-12-02T15:05:39ZCREB3L2-mediated expression of Sec23A/Sec24D is involved in hepatic stellate cell activation through ER-Golgi transport10.1038/s41598-017-08703-62045-2322https://doaj.org/article/962d23b9ba8644049160c4dea95063102017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08703-6https://doaj.org/toc/2045-2322Abstract 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.Shotaro TomoishiShinichi FukushimaKentaro ShinoharaToshiaki KatadaKota SaitoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Shotaro Tomoishi
Shinichi Fukushima
Kentaro Shinohara
Toshiaki Katada
Kota Saito
CREB3L2-mediated expression of Sec23A/Sec24D is involved in hepatic stellate cell activation through ER-Golgi transport
description Abstract 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.
format article
author Shotaro Tomoishi
Shinichi Fukushima
Kentaro Shinohara
Toshiaki Katada
Kota Saito
author_facet Shotaro Tomoishi
Shinichi Fukushima
Kentaro Shinohara
Toshiaki Katada
Kota Saito
author_sort Shotaro Tomoishi
title CREB3L2-mediated expression of Sec23A/Sec24D is involved in hepatic stellate cell activation through ER-Golgi transport
title_short CREB3L2-mediated expression of Sec23A/Sec24D is involved in hepatic stellate cell activation through ER-Golgi transport
title_full CREB3L2-mediated expression of Sec23A/Sec24D is involved in hepatic stellate cell activation through ER-Golgi transport
title_fullStr CREB3L2-mediated expression of Sec23A/Sec24D is involved in hepatic stellate cell activation through ER-Golgi transport
title_full_unstemmed CREB3L2-mediated expression of Sec23A/Sec24D is involved in hepatic stellate cell activation through ER-Golgi transport
title_sort creb3l2-mediated expression of sec23a/sec24d is involved in hepatic stellate cell activation through er-golgi transport
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/962d23b9ba8644049160c4dea9506310
work_keys_str_mv AT shotarotomoishi creb3l2mediatedexpressionofsec23asec24disinvolvedinhepaticstellatecellactivationthroughergolgitransport
AT shinichifukushima creb3l2mediatedexpressionofsec23asec24disinvolvedinhepaticstellatecellactivationthroughergolgitransport
AT kentaroshinohara creb3l2mediatedexpressionofsec23asec24disinvolvedinhepaticstellatecellactivationthroughergolgitransport
AT toshiakikatada creb3l2mediatedexpressionofsec23asec24disinvolvedinhepaticstellatecellactivationthroughergolgitransport
AT kotasaito creb3l2mediatedexpressionofsec23asec24disinvolvedinhepaticstellatecellactivationthroughergolgitransport
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