CD73: agent development potential and its application in diabetes and atherosclerosis

CD73, an important metabolic and immune escape-promoting gene, catalyzes the hydrolysis of adenosine monophosphate (AMP) to adenosine (ADO). AMP has anti-inflammatory and vascular relaxant properties, while ADO has a strong immunosuppressive effect, suggesting that CD73 has pro-inflammatory and immu...

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Main Authors: Dan Liu, Jingjing Zhao, Ling Li, Jie Wang, Chao Wang, Yudong Wu, Yucun Huang, Dongming Xing, Wujun Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1515875/full
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author Dan Liu
Jingjing Zhao
Ling Li
Jie Wang
Chao Wang
Yudong Wu
Yucun Huang
Dongming Xing
Dongming Xing
Wujun Chen
author_facet Dan Liu
Jingjing Zhao
Ling Li
Jie Wang
Chao Wang
Yudong Wu
Yucun Huang
Dongming Xing
Dongming Xing
Wujun Chen
author_sort Dan Liu
collection DOAJ
description CD73, an important metabolic and immune escape-promoting gene, catalyzes the hydrolysis of adenosine monophosphate (AMP) to adenosine (ADO). AMP has anti-inflammatory and vascular relaxant properties, while ADO has a strong immunosuppressive effect, suggesting that CD73 has pro-inflammatory and immune escape effects. However, CD73 also decreased proinflammatory reaction, suggesting that CD73 has a positive side to the body. Indeed, CD73 plays a protective role in diabetes, while with age, CD73 changes from anti-atherosclerosis to pro-atherosclerosis. The upregulation of CD73 with agents, including AGT-5, Aire-overexpressing DCs, Aspirin, BAFFR-Fc, CD4+ peptide, ICAs, IL-2 therapies, SAgAs, sCD73, stem cells, RAD51 inhibitor, TLR9 inhibitor, and VD, decreased diabetes and atherosclerosis development. However, the downregulation of CD73 with agents, including benzothiadiazine derivatives and CD73 siRNA, reduced atherosclerosis. Notably, many CD73 agents were investigated in clinical trials. However, no agents were used to treat diabetes and atherosclerosis. Most agents were CD73 inhibitors. Only FP-1201, a CD73 agonist, was investigated in clinical trials but its further development was discontinued. In addition, many lncRNAs, circRNAs, and genes are located at the same chromosomal location as CD73. In particular, circNT5E promoted CD73 expression. circNT5E may be a promising target for agent development. This mini-review focuses on the current state of knowledge of CD73 in diabetes, atherosclerosis, and its potential role in agent development.
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publishDate 2024-12-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj-art-b7e929fbe31c49edb7298a7289c90d842024-12-12T05:10:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.15158751515875CD73: agent development potential and its application in diabetes and atherosclerosisDan Liu0Jingjing Zhao1Ling Li2Jie Wang3Chao Wang4Yudong Wu5Yucun Huang6Dongming Xing7Dongming Xing8Wujun Chen9Guangdong Provincial People’s Hospital, Zhuhai Hospital (Jinwan Central Hospital of Zhuhai), Zhuhai, Guangdong, ChinaSleep Medicine Center, Huai’an No.3 People’s Hospital, Huaian Second Clinical College of Xuzhou Medical University, Huaian, ChinaDepartment of Pharmacy, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, ChinaThe Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong, ChinaThe Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong, ChinaThe Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong, ChinaGuangdong Provincial People’s Hospital, Zhuhai Hospital (Jinwan Central Hospital of Zhuhai), Zhuhai, Guangdong, ChinaThe Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong, ChinaSchool of Life Sciences, Tsinghua University, Beijing, ChinaThe Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong, ChinaCD73, an important metabolic and immune escape-promoting gene, catalyzes the hydrolysis of adenosine monophosphate (AMP) to adenosine (ADO). AMP has anti-inflammatory and vascular relaxant properties, while ADO has a strong immunosuppressive effect, suggesting that CD73 has pro-inflammatory and immune escape effects. However, CD73 also decreased proinflammatory reaction, suggesting that CD73 has a positive side to the body. Indeed, CD73 plays a protective role in diabetes, while with age, CD73 changes from anti-atherosclerosis to pro-atherosclerosis. The upregulation of CD73 with agents, including AGT-5, Aire-overexpressing DCs, Aspirin, BAFFR-Fc, CD4+ peptide, ICAs, IL-2 therapies, SAgAs, sCD73, stem cells, RAD51 inhibitor, TLR9 inhibitor, and VD, decreased diabetes and atherosclerosis development. However, the downregulation of CD73 with agents, including benzothiadiazine derivatives and CD73 siRNA, reduced atherosclerosis. Notably, many CD73 agents were investigated in clinical trials. However, no agents were used to treat diabetes and atherosclerosis. Most agents were CD73 inhibitors. Only FP-1201, a CD73 agonist, was investigated in clinical trials but its further development was discontinued. In addition, many lncRNAs, circRNAs, and genes are located at the same chromosomal location as CD73. In particular, circNT5E promoted CD73 expression. circNT5E may be a promising target for agent development. This mini-review focuses on the current state of knowledge of CD73 in diabetes, atherosclerosis, and its potential role in agent development.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1515875/fullCD73circNT5Ediabetesatherosclerosisagent development
spellingShingle Dan Liu
Jingjing Zhao
Ling Li
Jie Wang
Chao Wang
Yudong Wu
Yucun Huang
Dongming Xing
Dongming Xing
Wujun Chen
CD73: agent development potential and its application in diabetes and atherosclerosis
Frontiers in Immunology
CD73
circNT5E
diabetes
atherosclerosis
agent development
title CD73: agent development potential and its application in diabetes and atherosclerosis
title_full CD73: agent development potential and its application in diabetes and atherosclerosis
title_fullStr CD73: agent development potential and its application in diabetes and atherosclerosis
title_full_unstemmed CD73: agent development potential and its application in diabetes and atherosclerosis
title_short CD73: agent development potential and its application in diabetes and atherosclerosis
title_sort cd73 agent development potential and its application in diabetes and atherosclerosis
topic CD73
circNT5E
diabetes
atherosclerosis
agent development
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1515875/full
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