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image of Lysyl Oxidase as a Target to Reduce Graft Failure Post Solid Organ Transplantation, a Potential Target for Novel Treatment

Abstract

The present review was undertaken to clarify the potential role of the lysyl oxidase (Lox) family of enzymes in delaying graft dysfunction. Delayed graft failure is a well-known event that occurs post-transplantation period. Ischemia and trauma to the graft tissue before or during the operation procedures are likely to be the most important etiological causes of this complication. The lox proteins family including Lox and Lox- like proteins (LoxL1-4) are copper-dependent enzymes that catalyze the cross-linking of collagens to stabilize extracellular matrix (ECM). Hypoxia-induced factor 1-α (HIF-1α) and transforming growth factor β (TGF-β) are two upstream regulators of the Lox proteins family whose expression increased following hypoxia and tissue injury. Lox proteins’ overactivation upregulates several intracellular transduction pathways to promote oxidative stress (OS), ECM proteins accumulation, and epithelial to mesenchymal transition (EMT) contribute to vascular stiffness and tissue fibrogenesis, which increase the risk of graft failure post solid organ transplantation (SOT). Preclinical studies have shown that Lox protein inhibitors have the potential to prevent organ fibrosis. Regarding the molecular effects of Lox proteins in causing tissue fibrosis, these molecules can be further investigated as a drug target in reducing the possibility of organ fibrosis after allograft transplantation.

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2025-01-30
2025-09-08

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/content/journals/cmc/10.2174/0109298673346346241211063452
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Lysyl Oxidase as a Target to Reduce Graft Failure Post Solid Organ Transplantation, a Potential Target for Novel Treatment
Bentham Science Publishers ; https://doi.org/10.2174/0109298673346346241211063452
/content/journals/cmc/10.2174/0109298673346346241211063452
/content/journals/cmc/10.2174/0109298673346346241211063452
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  • Article Type:     Review Article
Keywords: hypoxia ; solid organ transplantation ; tissue injury ; lysyl oxidase-like protein ; hypoxia-induced factor 1-α ; transforming growth factor β ; graft failure ; Lysyl oxidase ; epithelial to mesenchymal transition

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