Lysyl oxidases: Emerging biomarkers and therapeutic targets for various diseases
Therapeutic targeting of extracellular proteins has attracted huge attention in treating human diseases. The lysyl oxidases (LOXs) are a family of secreted copper-dependent enzymes which initiate the covalent crosslinking of collagen and elastin fibers in the extracellular microenvironment, thereby...
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doaj-03efb38ef38f4222b57e52b94dc331022021-05-20T07:44:09ZengElsevierBiomedicine & Pharmacotherapy0753-33222020-11-01131110791Lysyl oxidases: Emerging biomarkers and therapeutic targets for various diseasesNan Yang0Dan-Feng Cao1Xi-Xi Yin2Hong-Hao Zhou3Xiao-Yuan Mao4Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha, 410078, PR China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha, 410078, PR China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, 410008, Hunan, PR ChinaXiangya International Academy of Translational Medicine, Central South University, Changsha, Hunan, 410013, PR ChinaDepartment of Pediatrics, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, PR ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha, 410078, PR China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha, 410078, PR China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, 410008, Hunan, PR ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha, 410078, PR China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha, 410078, PR China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, 410008, Hunan, PR China; Corresponding author at: Department of Clinical Pharmacology, Xiangya Hospital and Institute of Clinical Pharmacology, Central South University, Changsha, 410008, PR China.Therapeutic targeting of extracellular proteins has attracted huge attention in treating human diseases. The lysyl oxidases (LOXs) are a family of secreted copper-dependent enzymes which initiate the covalent crosslinking of collagen and elastin fibers in the extracellular microenvironment, thereby facilitating extracellular matrix (ECM) remodeling and ECM homeostasis. Apart from ECM-dependent roles, LOXs are also involved in other biological processes such as epithelial-to-mesenchymal transition (EMT) and transcriptional regulation, especially following hypoxic stress. Dysregulation of LOXs is found to underlie the onset and progression of multiple pathologies, such as carcinogenesis and cancer metastasis, fibrotic diseases, neurodegeneration and cardiovascular diseases. In this review, we make a comprehensive summarization of clinical and experimental evidences that support roles of for LOXs in disease pathology and points out LOXs as promising therapeutic targets for improving prognosis. Additionally, we also propose that LOXs reshape cell-ECM interaction or cell-cell interaction due to ECM-dependent and ECM-independent roles for LOXs. Therapeutic intervention of LOXs may have advantages in the maintenance of communication between ECM and cell or intercellular signaling, finally recovering organ function.http://www.sciencedirect.com/science/article/pii/S0753332220309847Lysyl oxidasesExtracellular matrix remodelingHypoxiaEpithelial-to-mesenchymal transitionDisease pathologyTherapeutic target |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nan Yang Dan-Feng Cao Xi-Xi Yin Hong-Hao Zhou Xiao-Yuan Mao |
spellingShingle |
Nan Yang Dan-Feng Cao Xi-Xi Yin Hong-Hao Zhou Xiao-Yuan Mao Lysyl oxidases: Emerging biomarkers and therapeutic targets for various diseases Biomedicine & Pharmacotherapy Lysyl oxidases Extracellular matrix remodeling Hypoxia Epithelial-to-mesenchymal transition Disease pathology Therapeutic target |
author_facet |
Nan Yang Dan-Feng Cao Xi-Xi Yin Hong-Hao Zhou Xiao-Yuan Mao |
author_sort |
Nan Yang |
title |
Lysyl oxidases: Emerging biomarkers and therapeutic targets for various diseases |
title_short |
Lysyl oxidases: Emerging biomarkers and therapeutic targets for various diseases |
title_full |
Lysyl oxidases: Emerging biomarkers and therapeutic targets for various diseases |
title_fullStr |
Lysyl oxidases: Emerging biomarkers and therapeutic targets for various diseases |
title_full_unstemmed |
Lysyl oxidases: Emerging biomarkers and therapeutic targets for various diseases |
title_sort |
lysyl oxidases: emerging biomarkers and therapeutic targets for various diseases |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2020-11-01 |
description |
Therapeutic targeting of extracellular proteins has attracted huge attention in treating human diseases. The lysyl oxidases (LOXs) are a family of secreted copper-dependent enzymes which initiate the covalent crosslinking of collagen and elastin fibers in the extracellular microenvironment, thereby facilitating extracellular matrix (ECM) remodeling and ECM homeostasis. Apart from ECM-dependent roles, LOXs are also involved in other biological processes such as epithelial-to-mesenchymal transition (EMT) and transcriptional regulation, especially following hypoxic stress. Dysregulation of LOXs is found to underlie the onset and progression of multiple pathologies, such as carcinogenesis and cancer metastasis, fibrotic diseases, neurodegeneration and cardiovascular diseases. In this review, we make a comprehensive summarization of clinical and experimental evidences that support roles of for LOXs in disease pathology and points out LOXs as promising therapeutic targets for improving prognosis. Additionally, we also propose that LOXs reshape cell-ECM interaction or cell-cell interaction due to ECM-dependent and ECM-independent roles for LOXs. Therapeutic intervention of LOXs may have advantages in the maintenance of communication between ECM and cell or intercellular signaling, finally recovering organ function. |
topic |
Lysyl oxidases Extracellular matrix remodeling Hypoxia Epithelial-to-mesenchymal transition Disease pathology Therapeutic target |
url |
http://www.sciencedirect.com/science/article/pii/S0753332220309847 |
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