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靶向粒钙蛋白可通过改善糖尿病血管生成加速伤口愈合。

Targeting Grancalcin Accelerates Wound Healing by Improving Angiogenesis in Diabetes.

机构信息

Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.

National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, 410008, China.

出版信息

Adv Sci (Weinh). 2024 Apr;11(14):e2305856. doi: 10.1002/advs.202305856. Epub 2024 Feb 2.

DOI:10.1002/advs.202305856
PMID:38308197
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11005700/
Abstract

Chronic 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.

摘要

慢性糖尿病性伤口是糖尿病的一种严重并发症，常导致截肢和高死亡率。伤口中的促炎分泌组持续促进血管生成缺陷，并导致组织修复失调。本研究旨在设计一种明胶甲基丙烯酰胺（GelMA）水凝胶，以持续释放粒联蛋白中和抗体（GCA-NAb），并将其评估为促进糖尿病伤口愈合的潜在支架。结果表明，在糖尿病溃疡个体和动物的伤口部位，骨源性免疫细胞分泌的蛋白粒联蛋白（GCA）的表达升高。GCA 表达的遗传抑制加速了动物模型中的血管生成和愈合。机制研究表明，粒联蛋白与瞬时受体电位 melastatin 8（TRPM8）结合，并部分使下游信号通路失活，从而损害体外和离体的血管生成。GCA-NAb 的全身或局部给药可加速糖尿病小鼠的伤口修复。数据表明，GCA 是治疗糖尿病性溃疡的潜在治疗靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/818c/11005700/03fc13f683cb/ADVS-11-2305856-g005.jpg
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