Hypoxic microenvironment promotes diabetic wound healing by polarizing macrophages to the M2 phenotype in vivo

IF 2.9 4区 生物学 Q3 CELL BIOLOGY
Feiyu Cai, Peng Wang, Mengling Yuan, Wenjiao Chen, Yi Liu
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Abstract

Background

In diabetic wounds, M2 polarization of macrophages regulates the transition from an inflammatory phase to a proliferative phase. Prior investigations have demonstrated the potential of deferoxamine (DFO) in creating a localized hypoxic microenvironment, which could stimulate angiogenesis by promoting vascular endothelial growth factor (VEGF) secretion in diabetic wound healing. Nevertheless, there is still no clear information on whether this chemically induced hypoxic microenvironment modulates macrophage polarization to promote diabetic wound healing.

Methods

The 18 diabetic mice were randomly divided into three groups: a control group (n = 6), a 100µM DFO group (n = 6), and a 200µM DFO group (n = 6). Subsequently, a full-thickness wound with a diameter of 1.00 cm was created on the dorsal region of the diabetic mice. Observe wound closure regularly during treatment. At the end of the observation, tissue specimens were collected for a series of experiments and analyses, including hematoxylin and eosin (H&E), Masson, immunofluorescent, and immunohistochemical staining. The role and mechanism of DFO in regulating macrophage polarization were studied using RAW264.7 cells.

Results

In comparison to the control group, the administration of DFO notably facilitates wound healing in diabetic mice. In diabetic wounds, DFO increases blood supply by upregulating VEGF, which promotes angiogenesis. Additionally, The expression of HSP70 and CD206 were also upregulated by DFO in both vivo and in vitro, while iNOS expression was downregulated. Additionally, knk437 inhibited the expression of HSP70 in RAW264.7 cells, resulting in a reduction of M2 polarization and an increase in M1 polarization.

Conclusion

The induction of a hypoxic microenvironment by DFO has been found to exert a substantial influence on the process of diabetic wound healing. DFO treatment enhances the capacity of diabetic wounds to stimulate angiogenesis and modulate macrophage polarization that may be associated with HSP70 expression, thereby expediting the transition of these wounds from an inflammatory to a proliferative state.

Abstract Image

Abstract Image

缺氧微环境通过在体内将巨噬细胞极化为 M2 表型,促进糖尿病伤口愈合。
背景:在糖尿病伤口中,巨噬细胞的 M2 极化调节着从炎症阶段向增殖阶段的过渡。先前的研究表明,去氧胺(DFO)可创造局部缺氧微环境,通过促进糖尿病伤口愈合过程中血管内皮生长因子(VEGF)的分泌来刺激血管生成。然而,关于这种化学诱导的缺氧微环境是否会调节巨噬细胞极化以促进糖尿病伤口愈合,目前还没有明确的信息:方法:将 18 只糖尿病小鼠随机分为三组:对照组(n = 6)、100µM DFO 组(n = 6)和 200µM DFO 组(n = 6)。随后,在糖尿病小鼠背侧创建一个直径为 1.00 厘米的全厚伤口。治疗期间定期观察伤口闭合情况。观察结束后,收集组织标本进行一系列实验和分析,包括苏木精和伊红(H&E)、Masson、免疫荧光和免疫组化染色。利用 RAW264.7 细胞研究了 DFO 调节巨噬细胞极化的作用和机制:结果:与对照组相比,服用 DFO 显著促进了糖尿病小鼠伤口的愈合。在糖尿病伤口中,DFO 通过上调血管内皮生长因子增加血液供应,从而促进血管生成。此外,DFO 还能在体内和体外上调 HSP70 和 CD206 的表达,同时下调 iNOS 的表达。此外,knk437 还能抑制 HSP70 在 RAW264.7 细胞中的表达,导致 M2 极化减少,M1 极化增加:结论:研究发现,DFO 诱导的缺氧微环境对糖尿病伤口愈合过程产生了重大影响。DFO治疗增强了糖尿病伤口刺激血管生成和调节巨噬细胞极化的能力,这可能与HSP70的表达有关,从而加快了这些伤口从炎症状态向增殖状态的转变。
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来源期刊
Journal of Molecular Histology
Journal of Molecular Histology 生物-细胞生物学
CiteScore
5.90
自引率
0.00%
发文量
68
审稿时长
1 months
期刊介绍: The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.
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