Thyroid Hormone Protects Human Lung Epithelial Cells from Cold Preservation and Warm Reperfusion-induced Injury

Overview

Journal J Transl Med

Publisher Biomed Central

Specialties Biomedical Engineering
General Medicine

Date 2024 Mar 1

PMID 38429788

Authors

Dejan Bojic

Tanroop Aujla

Junichi Sugihara

Aaron Wong

Shaf Keshavjee

Mingyao Liu

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

The impact of hormones on lung development and function: an overlooked aspect to consider from early childhood.

Pelizzo G, Calcaterra V, Baldassarre P, Marinaro M, Taranto S, Ceresola M Front Endocrinol (Lausanne). 2024; 15:1425149.

PMID: 39371928 PMC: 11449876. DOI: 10.3389/fendo.2024.1425149.

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