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A Multifunctional Role of Leucine-Rich α-2-Glycoprotein 1 in Cutaneous Wound Healing Under Normal and Diabetic Conditions
Delayed wound healing is commonly associated with diabetes. It may lead to amputation and death if not treated in a timely fashion. Limited treatments are available partially due to the poor understanding of the complex disease pathophysiology. Here, we investigated the role of leucine-rich α-2-glyc...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576570/ https://www.ncbi.nlm.nih.gov/pubmed/32887674 http://dx.doi.org/10.2337/db20-0585 |
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author | Liu, Chenghao Teo, Melissa Hui Yen Pek, Sharon Li Ting Wu, Xiaoting Leong, Mei Ling Tay, Hui Min Hou, Han Wei Ruedl, Christiane Moss, Stephen E. Greenwood, John Tavintharan, Subramaniam Hong, Wanjin Wang, Xiaomeng |
author_facet | Liu, Chenghao Teo, Melissa Hui Yen Pek, Sharon Li Ting Wu, Xiaoting Leong, Mei Ling Tay, Hui Min Hou, Han Wei Ruedl, Christiane Moss, Stephen E. Greenwood, John Tavintharan, Subramaniam Hong, Wanjin Wang, Xiaomeng |
author_sort | Liu, Chenghao |
collection | PubMed |
description | Delayed wound healing is commonly associated with diabetes. It may lead to amputation and death if not treated in a timely fashion. Limited treatments are available partially due to the poor understanding of the complex disease pathophysiology. Here, we investigated the role of leucine-rich α-2-glycoprotein 1 (LRG1) in normal and diabetic wound healing. First, our data showed that LRG1 was significantly increased at the inflammation stage of murine wound healing, and bone marrow–derived cells served as a major source of LRG1. LRG1 deletion causes impaired immune cell infiltration, reepithelialization, and angiogenesis. As a consequence, there is a significant delay in wound closure. On the other hand, LRG1 was markedly induced in diabetic wounds in both humans and mice. LRG1-deficient mice were resistant to diabetes-induced delay in wound repair. We further demonstrated that this could be explained by the mitigation of increased neutrophil extracellular traps (NETs) in diabetic wounds. Mechanistically, LRG1 mediates NETosis in an Akt-dependent manner through TGFβ type I receptor kinase ALK5. Taken together, our studies demonstrated that LRG1 derived from bone marrow cells is required for normal wound healing, revealing a physiological role for this glycoprotein, but that excess LRG1 expression in diabetes is pathogenic and contributes to chronic wound formation. |
format | Online Article Text |
id | pubmed-7576570 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-75765702020-11-02 A Multifunctional Role of Leucine-Rich α-2-Glycoprotein 1 in Cutaneous Wound Healing Under Normal and Diabetic Conditions Liu, Chenghao Teo, Melissa Hui Yen Pek, Sharon Li Ting Wu, Xiaoting Leong, Mei Ling Tay, Hui Min Hou, Han Wei Ruedl, Christiane Moss, Stephen E. Greenwood, John Tavintharan, Subramaniam Hong, Wanjin Wang, Xiaomeng Diabetes Complications Delayed wound healing is commonly associated with diabetes. It may lead to amputation and death if not treated in a timely fashion. Limited treatments are available partially due to the poor understanding of the complex disease pathophysiology. Here, we investigated the role of leucine-rich α-2-glycoprotein 1 (LRG1) in normal and diabetic wound healing. First, our data showed that LRG1 was significantly increased at the inflammation stage of murine wound healing, and bone marrow–derived cells served as a major source of LRG1. LRG1 deletion causes impaired immune cell infiltration, reepithelialization, and angiogenesis. As a consequence, there is a significant delay in wound closure. On the other hand, LRG1 was markedly induced in diabetic wounds in both humans and mice. LRG1-deficient mice were resistant to diabetes-induced delay in wound repair. We further demonstrated that this could be explained by the mitigation of increased neutrophil extracellular traps (NETs) in diabetic wounds. Mechanistically, LRG1 mediates NETosis in an Akt-dependent manner through TGFβ type I receptor kinase ALK5. Taken together, our studies demonstrated that LRG1 derived from bone marrow cells is required for normal wound healing, revealing a physiological role for this glycoprotein, but that excess LRG1 expression in diabetes is pathogenic and contributes to chronic wound formation. American Diabetes Association 2020-11 2020-09-04 /pmc/articles/PMC7576570/ /pubmed/32887674 http://dx.doi.org/10.2337/db20-0585 Text en © 2020 by the American Diabetes Association https://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license. |
spellingShingle | Complications Liu, Chenghao Teo, Melissa Hui Yen Pek, Sharon Li Ting Wu, Xiaoting Leong, Mei Ling Tay, Hui Min Hou, Han Wei Ruedl, Christiane Moss, Stephen E. Greenwood, John Tavintharan, Subramaniam Hong, Wanjin Wang, Xiaomeng A Multifunctional Role of Leucine-Rich α-2-Glycoprotein 1 in Cutaneous Wound Healing Under Normal and Diabetic Conditions |
title | A Multifunctional Role of Leucine-Rich α-2-Glycoprotein 1 in Cutaneous Wound Healing Under Normal and Diabetic Conditions |
title_full | A Multifunctional Role of Leucine-Rich α-2-Glycoprotein 1 in Cutaneous Wound Healing Under Normal and Diabetic Conditions |
title_fullStr | A Multifunctional Role of Leucine-Rich α-2-Glycoprotein 1 in Cutaneous Wound Healing Under Normal and Diabetic Conditions |
title_full_unstemmed | A Multifunctional Role of Leucine-Rich α-2-Glycoprotein 1 in Cutaneous Wound Healing Under Normal and Diabetic Conditions |
title_short | A Multifunctional Role of Leucine-Rich α-2-Glycoprotein 1 in Cutaneous Wound Healing Under Normal and Diabetic Conditions |
title_sort | multifunctional role of leucine-rich α-2-glycoprotein 1 in cutaneous wound healing under normal and diabetic conditions |
topic | Complications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576570/ https://www.ncbi.nlm.nih.gov/pubmed/32887674 http://dx.doi.org/10.2337/db20-0585 |
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