Item request has been placed!
×
Item request cannot be made.
×
Processing Request
Immortalized mesenchymal stromal cells overexpressing alpha-1 antitrypsin protect acinar cells from apoptotic and ferroptotic cell death.
Item request has been placed!
×
Item request cannot be made.
×
Processing Request
- Additional Information
- Source:
Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101083777 Publication Model: Print Cited Medium: Internet ISSN: 1582-4934 (Electronic) Linking ISSN: 15821838 NLM ISO Abbreviation: J Cell Mol Med Subsets: MEDLINE
- Publication Information:
Publication: Oxford, England : Wiley-Blackwell
Original Publication: Bucharest : "Carol Davila" University Press, 2000-
- Subject Terms:
- Abstract:
Chronic pancreatitis (CP) is a progressive inflammatory disorder that impairs endocrine and exocrine function. Our previous work showed that mesenchymal stem/stromal cells (MSCs) and MSCs overexpressing alpha-1 antitrypsin (AAT-MSCs) could be therapeutic tools for CP. However, primary MSCs are predisposed to undergo senescence during culture expansion, which limits their therapeutic applications. We generated and characterized immortalized human MSCs (iMSCs) and AAT-MSCs (iAAT-MSCs) and tested their protective effect on 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced acinar cell death in an in vitro cell culture system. Primary MSCs were immortalized by transduction with simian virus 40 large T antigen (SV40LT), and the resulting iMSC and iAAT-MSC lines were analysed for proliferation, senescence, phenotype and multi-differentiation potential. Subsequently, apoptosis and ferroptosis pathways were investigated by assessing changes before and after TNBS treatment. Coculture of iMSCs and iAAT-MSCs with acinar cell lines inhibited early cell death induced by TNBS, reduced ER stress and reversed TNBS-induced protein reduction at tight junctions. Additionally, iMSCs and iAAT-MSCs exerted such protection by regulating mitochondrial respiration, ATP content and ROS production in TNBS-induced acinar cells. Furthermore, iMSCs and iAAT-MSCs ameliorated TNBS-induced ferroptosis by modulating iron generation and ROS production and regulating the ferritin heavy chain 1 (FTH1)/protein disulfide isomerase (PDI)/glutathione peroxide 4 (GPX4) signalling pathways in acinar cells. These findings identify ferroptosis as an unrecognized mechanism that leads to TNBS-induced cell death and offer mechanistic insights relevant to using stem cell therapy to treat acinar cell death associated with CP.
(© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
- Comments:
Update of: Res Sq. 2023 Aug 09:rs.3.rs-2961444. doi: 10.21203/rs.3.rs-2961444/v1. (PMID: 37609340)
- References:
Heliyon. 2024 Feb 03;10(3):e25251. (PMID: 38356500)
Cell Death Dis. 2019 Sep 10;10(9):662. (PMID: 31506423)
Biochem Pharmacol. 2015 Feb 15;93(4):449-60. (PMID: 25559498)
Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):448-53. (PMID: 10618438)
Bioengineered. 2021 Dec;12(1):1986-1996. (PMID: 34047671)
Gut. 2002 Apr;50(4):542-8. (PMID: 11889077)
Stem Cells Dev. 2014 Oct 1;23(19):2377-89. (PMID: 24857590)
Int J Mol Sci. 2023 Aug 12;24(16):. (PMID: 37628897)
Eur J Pain. 2010 Jul;14(6):595-601. (PMID: 20004601)
Mol Ther. 2017 Nov 1;25(11):2490-2501. (PMID: 28784560)
Chem Biol Interact. 2022 Oct 1;366:110148. (PMID: 36084724)
Acta Gastroenterol Belg. 2015 Jan-Mar;78(1):3-7. (PMID: 26118571)
Signal Transduct Target Ther. 2021 Feb 3;6(1):49. (PMID: 33536413)
J Cardiovasc Pharmacol. 2015 Jul;66(1):96-107. (PMID: 25815674)
Stem Cells Transl Med. 2021 Feb;10(2):320-331. (PMID: 32945622)
Mol Med Rep. 2017 Sep;16(3):3455-3460. (PMID: 28713987)
Stem Cell Reports. 2021 Apr 13;16(4):694-707. (PMID: 33636113)
Int J Mol Sci. 2016 May 24;17(6):. (PMID: 27231894)
Front Pharmacol. 2017 May 09;8:255. (PMID: 28536528)
Gastroenterology. 2011 Mar;140(3):998-1008. (PMID: 21130088)
J Intern Med. 2014 Oct;276(4):311-35. (PMID: 24661570)
Pancreas. 2000 Oct;21(3):296-304. (PMID: 11039475)
Niger J Physiol Sci. 2021 Jun 30;36(1):67-76. (PMID: 34987251)
Cell Death Dis. 2020 Feb 3;11(2):86. (PMID: 32015337)
Stem Cells Int. 2020 Jun 16;2020:5726947. (PMID: 32612662)
Free Radic Biol Med. 2019 Mar;133:144-152. (PMID: 30219704)
Hum Exp Toxicol. 2020 Apr;39(4):477-491. (PMID: 31835924)
Ann N Y Acad Sci. 2011 Dec;1240:E31-5. (PMID: 22360827)
Stem Cells Dev. 2013 Jan 15;22(2):268-78. (PMID: 22765508)
Mol Ther. 2017 Nov 1;25(11):2438-2439. (PMID: 29055621)
Arch Med Sci. 2020 Oct 12;17(4):1100-1108. (PMID: 34336038)
Stem Cells Transl Med. 2019 May;8(5):418-429. (PMID: 30680957)
Oxid Med Cell Longev. 2021 Jun 22;2021:6644576. (PMID: 34257815)
Sci Rep. 2020 Dec 3;10(1):21135. (PMID: 33273633)
J Cell Mol Med. 2024 Oct;28(20):e70093. (PMID: 39468387)
Sci Rep. 2018 Jun 12;8(1):8981. (PMID: 29895825)
Antioxidants (Basel). 2022 Dec 31;12(1):. (PMID: 36670963)
Diabetol Metab Syndr. 2022 Jun 27;14(1):89. (PMID: 35761309)
Int J Mol Med. 2020 Nov;46(5):1695-1706. (PMID: 33000213)
Int J Biol Sci. 2021 Mar 1;17(4):942-956. (PMID: 33867820)
STAR Protoc. 2020 Dec 30;2(1):100245. (PMID: 33458707)
Int J Mol Sci. 2021 Oct 01;22(19):. (PMID: 34639008)
Biomedicines. 2021 Nov 16;9(11):. (PMID: 34829924)
Exp Neurobiol. 2013 Dec;22(4):283-300. (PMID: 24465144)
J Nanobiotechnology. 2023 Aug 17;21(1):272. (PMID: 37592351)
Biochim Biophys Acta. 2016 Dec;1863(12):2977-2992. (PMID: 27646922)
Biochem Biophys Res Commun. 2021 Oct 8;573:48-54. (PMID: 34388454)
J Hazard Mater. 2020 Feb 15;384:121390. (PMID: 31735470)
Clin Cancer Res. 2017 Jun 15;23(12):2951-2960. (PMID: 27979915)
Mol Med Rep. 2020 Apr;21(4):1833-1840. (PMID: 32319628)
Biology (Basel). 2021 Dec 21;11(1):. (PMID: 35053007)
Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16242-7. (PMID: 18852471)
J Gastroenterol. 2008;43(6):473-83. (PMID: 18600392)
Int J Immunopathol Pharmacol. 2021 Jan-Dec;35:20587384211054036. (PMID: 34696610)
F1000Res. 2018 May 17;7:. (PMID: 29946424)
PLoS One. 2012;7(2):e31807. (PMID: 22359633)
Stem Cell Res. 2014 Mar;12(2):584-98. (PMID: 24561906)
- Grant Information:
R01DK125454 United States DK NIDDK NIH HHS; I01 BX004536 United States BX BLRD VA; VA-ORD BLR&D Merit I01BX004536) United States VA VA; R01DK120394 United States DK NIDDK NIH HHS; R01DK118529 United States DK NIDDK NIH HHS; R01DK105183 United States DK NIDDK NIH HHS; UG3DK136705 United States DK NIDDK NIH HHS
- Contributed Indexing:
Keywords: acinar cell death; chronic pancreatitis; ferroptosis; immortalized human MSCs
- Accession Number:
0 (alpha 1-Antitrypsin)
8T3HQG2ZC4 (Trinitrobenzenesulfonic Acid)
- Publication Date:
Date Created: 20241029 Date Completed: 20241029 Latest Revision: 20241105
- Publication Date:
20241105
- Accession Number:
PMC11518823
- Accession Number:
10.1111/jcmm.70093
- Accession Number:
39468387
No Comments.