Targeting Grancalcin Accelerates Wound Healing by Improving Angiogenesis in Diabetes
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Published:2024-02-02
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Volume:
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ISSN:2198-3844
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Container-title:Advanced Science
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language:en
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Short-container-title:Advanced Science
Author:
Xiang Peng12ORCID,
Jiang Meng12,
Chen Xin12,
Chen Linyun12,
Cheng Yalun12,
Luo Xianghang12,
Zhou Haiyan12,
Zheng Yongjun3ORCID
Affiliation:
1. Department of Endocrinology Endocrinology Research Center Xiangya Hospital of Central South University Changsha Hunan 410008 China
2. National Clinical Research Center for Geriatric Disorders Xiangya Hospital Changsha Hunan 410008 China
3. Department of Burn Surgery the First Affiliated Hospital of Naval Medical University Shanghai 200433 China
Abstract
AbstractChronic diabetic wounds are a serious complication of diabetes and often result in limb amputations and confer high mortality rates. The proinflammatory secretome in the wound perpetuates defective neovascularization and contributes to dysregulated tissue repair. This study aims to design a gelatin methacrylamide (GelMA) hydrogel to sustained the release of grancalcin‐neutralizing antibody (GCA‐NAb) and evaluate it as a potential scaffold to promote diabetic wound healing. Results show that the expression of grancalcin(GCA), a protein secreted by bone marrow‐derived immune cells, is elevated in the wound sites of individuals and animals with diabetic ulcers. Genetic inhibition of grancalcin expression accelerates vascularization and healing in an animal model. Mechanistic studies show that grancalcin binds to transient receptor potential melastatin 8(TRPM8) and partially inactivates its downstream signaling pathways, thereby impairing angiogenesis in vitro and ex vivo. Systemic or topical administration of a GCA‐NAb accelerate wound repair in mice with diabetes. The data suggest that GCA is a potential therapeutic target for the treatment of diabetic ulcers.
Funder
National Natural Science Foundation of China
National Key Research and Development Program of China
Science Fund for Distinguished Young Scholars of Hunan Province
Shanghai Rising-Star Program
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)