LRG1 Accelerates Wound Healing in Diabetic Rats by Promoting Angiogenesis via the Wnt/β-Catenin Signaling Pathway.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Accounts of Chemical Research Pub Date : 2024-12-01 Epub Date: 2022-02-21 DOI:10.1177/15347346221081610
Ping Yang, Shiyan Li, Hao Zhang, Xiaofeng Ding, Qian Tan
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引用次数: 0

Abstract

Patients with diabetic wounds may end with lower extremity amputation or death. Leucine-rich α-2-glycoprotein 1 (LRG1) is an effective regulator of angiogenesis and essential for timely wound healing. However, its role in regulating angiogenesis in diabetic wounds remains unclear. This study aimed to investigate the pro-angiogenic function of exogenous LRG1 in diabetic wound healing and explore possible mechanisms. LRG1 expression patterns following injury in normal and diabetic wounds were determined by western blotting. Local injection of LRG1 was used to verify the effects on angiogenesis and wound healing in diabetic rats. Immunohistochemical staining for CD31 was used to analyze the vessel density. Human umbilical vein endothelial cells (HUVECs) cultured in hyperglycemia were used to explore how LRG1 promotes angiogenesis in diabetic wound healing. We found that the expression peak of LRG1 around the wounds was delayed in diabetic rats compared with that in normal rats. Exogenous administration of LRG1 significantly accelerated the wound closure rate and promoted angiogenesis in diabetic rats. In addition, exogenous LRG1 effectively restored the proliferation, migration, and tube formation ability of HUVECs under hyperglycemia. Mechanistically, LRG1 promoted angiogenesis and diabetic wound healing mainly by activating the Wnt/β-catenin pathway, which is inhibited in diabetic wounds. This research suggests that LRG1 promotes angiogenesis and wound closure in diabetic rats by improving angiogenesis via activation of the Wnt/β-catenin pathway. Hence, LRG1 may be a possible therapeutic strategy for diabetic foot treatment.

LRG1通过Wnt/β-Catenin信号通路促进血管生成,从而加速糖尿病大鼠的伤口愈合
糖尿病患者的伤口可能会导致下肢截肢或死亡。富亮氨酸α-2-糖蛋白 1(LRG1)是血管生成的有效调节因子,对伤口的及时愈合至关重要。然而,它在糖尿病伤口血管生成中的调控作用仍不清楚。本研究旨在研究外源性 LRG1 在糖尿病伤口愈合中的促血管生成功能,并探索可能的机制。本研究采用免疫印迹法测定了正常伤口和糖尿病伤口损伤后 LRG1 的表达模式。采用局部注射 LRG1 的方法验证其对糖尿病大鼠血管生成和伤口愈合的影响。CD31 免疫组化染色用于分析血管密度。在高血糖条件下培养的人脐静脉内皮细胞(HUVECs)被用来探讨 LRG1 如何促进糖尿病伤口愈合中的血管生成。我们发现,与正常大鼠相比,糖尿病大鼠伤口周围 LRG1 的表达峰值延迟。外源性给予 LRG1 能明显加快糖尿病大鼠伤口的闭合速度并促进血管生成。此外,外源性 LRG1 还能有效恢复高血糖条件下 HUVECs 的增殖、迁移和血管形成能力。从机理上讲,LRG1主要通过激活Wnt/β-catenin通路促进血管生成和糖尿病伤口愈合,而糖尿病伤口的Wnt/β-catenin通路受到抑制。这项研究表明,LRG1 通过激活 Wnt/β-catenin 通路改善血管生成,从而促进糖尿病大鼠的血管生成和伤口闭合。因此,LRG1 可能是糖尿病足治疗的一种治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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