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Downregulation of a tumor suppressor gene LKB1 in lung transplantation as a biomarker for chronic murine lung allograft rejection.
- Source :
-
Cellular immunology [Cell Immunol] 2023 Apr; Vol. 386, pp. 104690. Date of Electronic Publication: 2023 Feb 16. - Publication Year :
- 2023
-
Abstract
- Background: We recently demonstrated decreased tumor suppressor gene liver kinase B1 (LKB1) level in lung transplant recipients diagnosed with bronchiolitis obliterans syndrome. STE20-related adaptor alpha (STRADα) functions as a pseudokinase that binds and regulates LKB1 activity.<br />Methods: A murine model of chronic lung allograft rejection in which a single lung from a B6D2F1 mouse was orthotopically transplanted into a DBA/2J mouse was employed. We examined the effect of LKB1 knockdown using CRISPR-CAS9 in vitro culture system.<br />Results: Significant downregulation of LKB1 and STRADα expression was found in donor lung compared to recipient lung. STRADα knockdown significantly inhibited LKB1, pAMPK expression but induced phosphorylated mammalian target of rapamycin (mTOR), fibronectin, and Collagen-I, expression in BEAS-2B cells. LKB1 overexpression decreased fibronectin, Collagen-I, and phosphorylated mTOR expression in A549 cells.<br />Conclusions: We demonstrated that downregulation of LKB1-STRADα pathway accompanied with increased fibrosis, results in development of chronic rejection following murine lung transplantation.<br />Competing Interests: Declaration of Competing Interest 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.<br /> (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Mice
Down-Regulation
Mice, Inbred DBA
Protein Serine-Threonine Kinases genetics
Protein Serine-Threonine Kinases metabolism
TOR Serine-Threonine Kinases metabolism
Lung metabolism
Biomarkers
Genes, Tumor Suppressor
Allografts
Collagen genetics
Collagen metabolism
Mammals genetics
Mammals metabolism
Fibronectins genetics
Fibronectins metabolism
Lung Transplantation
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2163
- Volume :
- 386
- Database :
- MEDLINE
- Journal :
- Cellular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 36812767
- Full Text :
- https://doi.org/10.1016/j.cellimm.2023.104690