Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2020
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
_version_ 1783598041792512000
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
work_keys_str_mv AT liuchenghao amultifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT teomelissahuiyen amultifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT peksharonliting amultifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT wuxiaoting amultifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT leongmeiling amultifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT tayhuimin amultifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT houhanwei amultifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT ruedlchristiane amultifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT mossstephene amultifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT greenwoodjohn amultifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT tavintharansubramaniam amultifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT hongwanjin amultifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT wangxiaomeng amultifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT liuchenghao multifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT teomelissahuiyen multifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT peksharonliting multifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT wuxiaoting multifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT leongmeiling multifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT tayhuimin multifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT houhanwei multifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT ruedlchristiane multifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT mossstephene multifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT greenwoodjohn multifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT tavintharansubramaniam multifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT hongwanjin multifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions
AT wangxiaomeng multifunctionalroleofleucinericha2glycoprotein1incutaneouswoundhealingundernormalanddiabeticconditions