The unique pancreatic stellate cell gene expression signatures are associated with the progression from acute to chronic pancreatitis

Chronic pancreatitis (CP) is characterized by irreversible fibro-inflammatory changes induced by pancreatic stellate cell (PSC). Unresolved or recurrent injury causes dysregulation of biological process following AP, which would cause CP. Here, we systematically identify genes whose expressions are...

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Autores principales:	Cheng Hu, Liyuan Yin, Zhiyao Chen, Richard T. Waldron, Aurelia Lugea, Yiyun Lin, Xiaoqian Zhai, Li Wen, Yuan-Ping Han, Stephen J. Pandol, Lihui Deng, Qing Xia
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Pancreatic stellate cell Acute pancreatitis Recurrent acute pancreatitis Chronic pancreatitis SPARC Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/e2404d6e0c284a32b752113efbf423bb
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spelling	oai:doaj.org-article:e2404d6e0c284a32b752113efbf423bb2021-12-04T04:33:33ZThe unique pancreatic stellate cell gene expression signatures are associated with the progression from acute to chronic pancreatitis2001-037010.1016/j.csbj.2021.11.031https://doaj.org/article/e2404d6e0c284a32b752113efbf423bb2021-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2001037021004967https://doaj.org/toc/2001-0370Chronic pancreatitis (CP) is characterized by irreversible fibro-inflammatory changes induced by pancreatic stellate cell (PSC). Unresolved or recurrent injury causes dysregulation of biological process following AP, which would cause CP. Here, we systematically identify genes whose expressions are unique to PSC by comparing transcriptome profiles among total pancreas, pancreatic stellate, acinar, islet and immune cells. We then identified candidate genes and correlated them with the pancreatic disease continuum by performing intersection analysis among total PSC and activated PSC genes, and genes persistently differentially expressed during acute pancreatitis (AP) recovery. Last, we examined the association between candidate genes and AP, and substantiated their potential as biomarkers in experimental AP and recurrent AP (RAP) models. A total of 68 genes were identified as highly and uniquely expressed in PSC. The PSC signatures were highly enriched with extracellular matrix remodeling genes and were significantly enriched in AP pancreas compared to healthy control tissues. Among PSC signature genes that comprised a fibrotic phenotype, 10 were persistently differentially expressed during AP recovery. SPARC was determined as a candidate marker for the pancreatic disease continuum, which was not only persistently differentially expressed even five days after AP injury, but also highly expressed in two clinical datasets of CP. Sparc was also validated as highly elevated in RAP compared to AP mice. This work highlights the unique transcriptional profiles of PSC. These PSC signatures’ expression may help to identify patients with high risk of AP progression to CP.Cheng HuLiyuan YinZhiyao ChenRichard T. WaldronAurelia LugeaYiyun LinXiaoqian ZhaiLi WenYuan-Ping HanStephen J. PandolLihui DengQing XiaElsevierarticlePancreatic stellate cellAcute pancreatitisRecurrent acute pancreatitisChronic pancreatitisSPARCBiotechnologyTP248.13-248.65ENComputational and Structural Biotechnology Journal, Vol 19, Iss , Pp 6375-6385 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pancreatic stellate cell Acute pancreatitis Recurrent acute pancreatitis Chronic pancreatitis SPARC Biotechnology TP248.13-248.65
spellingShingle	Pancreatic stellate cell Acute pancreatitis Recurrent acute pancreatitis Chronic pancreatitis SPARC Biotechnology TP248.13-248.65 Cheng Hu Liyuan Yin Zhiyao Chen Richard T. Waldron Aurelia Lugea Yiyun Lin Xiaoqian Zhai Li Wen Yuan-Ping Han Stephen J. Pandol Lihui Deng Qing Xia The unique pancreatic stellate cell gene expression signatures are associated with the progression from acute to chronic pancreatitis
description	Chronic pancreatitis (CP) is characterized by irreversible fibro-inflammatory changes induced by pancreatic stellate cell (PSC). Unresolved or recurrent injury causes dysregulation of biological process following AP, which would cause CP. Here, we systematically identify genes whose expressions are unique to PSC by comparing transcriptome profiles among total pancreas, pancreatic stellate, acinar, islet and immune cells. We then identified candidate genes and correlated them with the pancreatic disease continuum by performing intersection analysis among total PSC and activated PSC genes, and genes persistently differentially expressed during acute pancreatitis (AP) recovery. Last, we examined the association between candidate genes and AP, and substantiated their potential as biomarkers in experimental AP and recurrent AP (RAP) models. A total of 68 genes were identified as highly and uniquely expressed in PSC. The PSC signatures were highly enriched with extracellular matrix remodeling genes and were significantly enriched in AP pancreas compared to healthy control tissues. Among PSC signature genes that comprised a fibrotic phenotype, 10 were persistently differentially expressed during AP recovery. SPARC was determined as a candidate marker for the pancreatic disease continuum, which was not only persistently differentially expressed even five days after AP injury, but also highly expressed in two clinical datasets of CP. Sparc was also validated as highly elevated in RAP compared to AP mice. This work highlights the unique transcriptional profiles of PSC. These PSC signatures’ expression may help to identify patients with high risk of AP progression to CP.
format	article
author	Cheng Hu Liyuan Yin Zhiyao Chen Richard T. Waldron Aurelia Lugea Yiyun Lin Xiaoqian Zhai Li Wen Yuan-Ping Han Stephen J. Pandol Lihui Deng Qing Xia
author_facet	Cheng Hu Liyuan Yin Zhiyao Chen Richard T. Waldron Aurelia Lugea Yiyun Lin Xiaoqian Zhai Li Wen Yuan-Ping Han Stephen J. Pandol Lihui Deng Qing Xia
author_sort	Cheng Hu
title	The unique pancreatic stellate cell gene expression signatures are associated with the progression from acute to chronic pancreatitis
title_short	The unique pancreatic stellate cell gene expression signatures are associated with the progression from acute to chronic pancreatitis
title_full	The unique pancreatic stellate cell gene expression signatures are associated with the progression from acute to chronic pancreatitis
title_fullStr	The unique pancreatic stellate cell gene expression signatures are associated with the progression from acute to chronic pancreatitis
title_full_unstemmed	The unique pancreatic stellate cell gene expression signatures are associated with the progression from acute to chronic pancreatitis
title_sort	unique pancreatic stellate cell gene expression signatures are associated with the progression from acute to chronic pancreatitis
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/e2404d6e0c284a32b752113efbf423bb
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The unique pancreatic stellate cell gene expression signatures are associated with the progression from acute to chronic pancreatitis

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