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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2017
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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) |
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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 |
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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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1718388782349156352 |