The unique pancreatic stellate cell gene expression signatures are associated with the progression from acute to chronic pancreatitis.
Acute pancreatitis
Chronic pancreatitis
Pancreatic stellate cell
Recurrent acute pancreatitis
SPARC
Journal
Computational and structural biotechnology journal
ISSN: 2001-0370
Titre abrégé: Comput Struct Biotechnol J
Pays: Netherlands
ID NLM: 101585369
Informations de publication
Date de publication:
2021
2021
Historique:
received:
15
07
2021
revised:
16
11
2021
accepted:
20
11
2021
entrez:
23
12
2021
pubmed:
24
12
2021
medline:
24
12
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34938413
doi: 10.1016/j.csbj.2021.11.031
pii: S2001-0370(21)00496-7
pmc: PMC8649580
doi:
Types de publication
Journal Article
Langues
eng
Pagination
6375-6385Subventions
Organisme : NCI NIH HHS
ID : P01 CA236585
Pays : United States
Informations de copyright
© 2021 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.
Déclaration de conflit d'intérêts
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Références
J Gastroenterol. 2017 Aug;52(8):992-1000
pubmed: 28130705
Matrix Biol. 2001 Jan;19(8):816-27
pubmed: 11223341
Lancet Gastroenterol Hepatol. 2016 Nov;1(3):226-237
pubmed: 28404095
Biomaterials. 2019 Feb;192:355-367
pubmed: 30476717
Cancer Res. 2020 Jul 1;80(13):2861-2873
pubmed: 32393661
Pancreatology. 2018 Oct;18(7):734-741
pubmed: 30139658
Pancreas. 2011 Nov;40(8):1195-200
pubmed: 21926938
Cancer Lett. 2019 Oct 10;462:51-60
pubmed: 31352078
PLoS One. 2013;8(2):e54962
pubmed: 23408952
Lancet. 2020 Aug 15;396(10249):499-512
pubmed: 32798493
Gastroenterology. 2013 Jun;144(6):1210-9
pubmed: 23622130
Lancet. 2019 Jun 8;393(10188):2312-2321
pubmed: 31030981
Pancreatology. 2020 Jan;20(1):51-59
pubmed: 31791885
Nature. 2016 Aug 25;536(7617):479-83
pubmed: 27509858
EMBO J. 1998 Mar 16;17(6):1625-34
pubmed: 9501084
Alcohol Clin Exp Res. 2015 Nov;39(11):2123-33
pubmed: 26463405
Physiol Rev. 2021 Oct 1;101(4):1691-1744
pubmed: 33949875
Am J Pathol. 2010 Nov;177(5):2585-96
pubmed: 20934972
Pancreas. 2010 May 7;39(8):1254-1262
pubmed: 20467342
J Gene Med. 2008 Sep;10(9):993-1004
pubmed: 18615449
J Clin Oncol. 2007 Jan 20;25(3):319-25
pubmed: 17235047
Pancreas. 1986;1(5):421-9
pubmed: 2436216
Ann Surg. 2001 Dec;234(6):769-78; discussion 778-9
pubmed: 11729383
Ann Oncol. 2014 May;25(5):1025-32
pubmed: 24562449
Virchows Arch. 2002 Nov;441(5):466-74
pubmed: 12447677
Clin Gastroenterol Hepatol. 2009 Nov;7(11 Suppl):S15-7
pubmed: 19896091
Gastroenterology. 2013 Jun;144(6):1252-61
pubmed: 23622135
Physiol Genomics. 2009 Jul 9;38(2):196-204
pubmed: 19435834
Gastroenterology. 2013 Jun;144(6):1292-302
pubmed: 23622139
Am J Gastroenterol. 2009 Nov;104(11):2797-805; quiz 2806
pubmed: 19603011
Bioinformatics. 2016 Sep 15;32(18):2847-9
pubmed: 27207943
Clin Gastroenterol Hepatol. 2008 Oct;6(10):1155-61
pubmed: 18639493
Sci Rep. 2021 Jan 14;11(1):1367
pubmed: 33446814
Cancer Sci. 2009 Dec;100(12):2309-17
pubmed: 19735487
Best Pract Res Clin Gastroenterol. 2010 Jun;24(3):349-58
pubmed: 20510834
Pancreas. 2009 Oct;38(7):752-7
pubmed: 19506532
Gastroenterology. 2016 Dec;151(6):1206-1217
pubmed: 27769811
PLoS One. 2014 Sep 02;9(9):e106397
pubmed: 25181531
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Gastroenterology. 2007 Apr;132(4):1557-73
pubmed: 17466744
Am J Gastroenterol. 2020 Mar;115(3):322-339
pubmed: 32022720
Arthritis Rheum. 2006 Aug;54(8):2626-31
pubmed: 16871529
EBioMedicine. 2020 Aug;58:102920
pubmed: 32739869
Pancreas. 2019 Aug;48(7):868-875
pubmed: 31268977
Sci Rep. 2018 Jan 15;8(1):725
pubmed: 29335425
Am J Physiol Gastrointest Liver Physiol. 2011 May;300(5):G739-48
pubmed: 21311029
Nat Rev Dis Primers. 2020 Jan 6;6(1):1
pubmed: 31907359
Sci Rep. 2018 Jan 23;8(1):1406
pubmed: 29362419
BMC Bioinformatics. 2013 Jan 16;14:7
pubmed: 23323831
Cell. 2014 Sep 25;159(1):80-93
pubmed: 25259922
J Transl Med. 2020 Nov 7;18(1):420
pubmed: 33160365
J Gastroenterol. 2019 Oct;54(10):928-935
pubmed: 31270692
Am J Gastroenterol. 2012 Jul;107(7):1096-103
pubmed: 22613906