Thyroid hormone protects human lung epithelial cells from cold preservation and warm reperfusion-induced injury.

Publisher: BioMed Central Country of Publication: England NLM ID: 101190741 Publication Model: Electronic Cited Medium: Internet ISSN: 1479-5876 (Electronic) Linking ISSN: 14795876 NLM ISO Abbreviation: J Transl Med Subsets: MEDLINE

Original Publication: [London] : BioMed Central, 2003-

Organ Preservation*/methods ; Reperfusion Injury*; Humans ; Mice ; Animals ; Lung/metabolism ; Reperfusion ; Epithelial Cells/metabolism ; Thyroid Hormones/pharmacology ; Thyroid Hormones/metabolism

Background: Cellular stress associated with static-cold storage (SCS) and warm reperfusion of donor lungs can contribute to ischemia-reperfusion (IR) injury during transplantation. Adding cytoprotective agents to the preservation solution may be conducive to reducing graft deterioration and improving post-transplant outcomes.
Methods: SCS and warm reperfusion were simulated in human lung epithelial cells (BEAS-2B) by exposing cells to low potassium dextran glucose solution at 4 °C for different periods and then switching back to serum-containing culture medium at 37 °C. Transcriptomic analysis was used to explore potential cytoprotective agents. Based on its results, cell viability, caspase activity, cell morphology, mitochondrial function, and inflammatory gene expression were examined under simulated IR conditions with or without thyroid hormones (THs).
Results: After 18 h SCS followed by 2 h warm reperfusion, genes related to inflammation and cell death were upregulated, and genes related to protein synthesis and metabolism were downregulated in BEAS-2B cells, which closely mirrored gene profiles found in thyroid glands of mice with congenital hypothyroidism. The addition of THs (T3 or T4) to the preservation solution increases cell viability, inhibits activation of caspase 3, 8 and 9, preserves cell morphology, enhances mitochondrial membrane potential, reduces mitochondrial superoxide production, and suppresses inflammatory gene expression.
Conclusion: Adding THs to lung preservation solutions may protect lung cells during SCS by promoting mitochondrial function, reducing apoptosis, and inhibiting pro-inflammatory pathways. Further in vivo testing is warranted to determine the potential clinical application of adding THs as therapeutics in lung preservation solutions.
(© 2024. The Author(s).)

J Thorac Cardiovasc Surg. 2016 Mar;151(3):861-869. (PMID: 26725713)
J Heart Lung Transplant. 2022 Aug;41(8):1003-1013. (PMID: 35710485)
Acta Biochim Pol. 2018;65(1):9-15. (PMID: 29352749)
Lancet Respir Med. 2013 Jun;1(4):318-28. (PMID: 24429157)
Int J Mol Sci. 2021 Oct 13;22(20):. (PMID: 34681708)
Am J Respir Crit Care Med. 2003 Feb 15;167(4):490-511. (PMID: 12588712)
Mol Cell Endocrinol. 2011 Jun 6;339(1-2):54-62. (PMID: 21458530)
J Appl Physiol (1985). 2000 Oct;89(4):1553-60. (PMID: 11007595)
Am J Transplant. 2005 Feb;5(2):292-9. (PMID: 15643988)
J Thorac Cardiovasc Surg. 2001 Mar;121(3):594-6. (PMID: 11241101)
Am J Respir Crit Care Med. 2000 Nov;162(5):1932-9. (PMID: 11069837)
Basic Res Cardiol. 2009 Jan;104(1):69-77. (PMID: 19101750)
Am J Physiol Lung Cell Mol Physiol. 2021 Jun 1;320(6):L979-L989. (PMID: 33688744)
Ann Surg. 2000 Mar;231(3):424-31. (PMID: 10714636)
J Physiol Biochem. 2015 Mar;71(1):99-106. (PMID: 25649359)
Transplantation. 2014 Nov 27;98(10):1119-27. (PMID: 25405914)
Sci Transl Med. 2021 Sep 15;13(611):eabf7601. (PMID: 34524862)
Biochem Biophys Res Commun. 2017 Jan 15;482(3):426-431. (PMID: 28212726)
J Heart Lung Transplant. 2014 Mar;33(3):309-15. (PMID: 24365768)
Cells. 2022 Mar 12;11(6):. (PMID: 35326426)
Semin Thorac Cardiovasc Surg. 2004 Winter;16(4):300-8. (PMID: 15635534)
Trials. 2021 Nov 27;22(1):852. (PMID: 34838132)
J Biol Chem. 2006 Jul 28;281(30):20666-20672. (PMID: 16717100)
Acta Pharmacol Sin. 2018 May;39(5):845-857. (PMID: 29565040)
Eur Respir J. 2020 Apr 9;55(4):. (PMID: 32060066)
J Surg Res. 2012 Dec;178(2):646-56. (PMID: 22727940)
J Surg Res. 2020 Sep;253:272-279. (PMID: 32402852)
J Heart Lung Transplant. 2013 Aug;32(8):823-31. (PMID: 23747218)
Clin Neurol Neurosurg. 2018 Feb;165:96-102. (PMID: 29331874)
J Thorac Cardiovasc Surg. 1989 Oct;98(4):529-34. (PMID: 2477644)
J Mol Cell Cardiol. 2005 Nov;39(5):841-4. (PMID: 16171808)
Nanoscale. 2015 Aug 7;7(29):12356-60. (PMID: 26151444)
Surgery. 2014 Mar;155(3):554-61. (PMID: 24439746)
Cells. 2021 Oct 10;10(10):. (PMID: 34685693)
Thyroid. 2011 Aug;21(8):879-90. (PMID: 21745103)
Front Biosci (Landmark Ed). 2009 Jan 01;14(10):3750-70. (PMID: 19273308)
Hepatology. 2007 Jan;45(1):170-7. (PMID: 17187421)
N Engl J Med. 2023 Nov 30;389(22):2029-2038. (PMID: 38048188)
Physiol Rev. 2014 Apr;94(2):355-82. (PMID: 24692351)
Biochim Biophys Acta. 2013 Jul;1830(7):3908-16. (PMID: 22484490)
Transplant Proc. 2009 Jul-Aug;41(6):2073-5. (PMID: 19715835)
Am J Transplant. 2019 May;19(5):1464-1477. (PMID: 30582269)
Am J Physiol Lung Cell Mol Physiol. 2018 Oct 1;315(4):L595-L608. (PMID: 30024306)

MOP-119514 Canada CIHR; PJT-148847 Canada CIHR

Keywords: Bioinformatics; Donor lung preservation; Inflammatory response; Mitochondrial function; Static cold storage

0 (Thyroid Hormones)

Date Created: 20240301 Date Completed: 20240304 Latest Revision: 20240711

20250114

PMC10908176

10.1186/s12967-024-05024-x

38429788