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肝细胞生长因子通过改变肠道巨噬细胞表型改善葡聚糖硫酸钠诱导的小鼠结肠炎。

Hepatocyte growth factor ameliorates dextran sodium sulfate‑induced colitis in a mouse model by altering the phenotype of intestinal macrophages.

机构信息

Division of Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8544, Japan.

出版信息

Mol Med Rep. 2023 Mar;27(3). doi: 10.3892/mmr.2023.12957. Epub 2023 Feb 17.

Abstract

Hepatocyte growth factor (HGF) serves key roles in cell motility, proliferation and immunoregulatory functions. However, the effect of HGF on macrophages is unclear. The present study aimed to elucidate the effect of HGF on the phenotypic alterations of intestinal lamina propria mononuclear cells (LPMCs). Colitis was induced in a mouse model using dextran sodium sulfate (DSS). Subsequently, LPMCs were isolated from the mice with chronic colitis and the expression levels of cytokine‑encoding genes in the LPMCs were determined. CD11b‑positive macrophages isolated from LPMCs were cultured with HGF, and alterations in the levels of M1 or M2 markers were evaluated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and flow cytometry. In addition, the cytokine levels were assessed using RT‑qPCR and ELISA. HGF shifted the phenotype of macrophages from M1 to M2‑like, as determined by increased mRNA expression levels of arginase‑1, CD206 and IL‑10, and reduced mRNA expression levels of CD86 and IL‑6 in mice with DSS‑induced colitis. Moreover, HGF could ameliorate DSS‑induced colitis owing to its immunosuppressive effect on immune cells. These findings indicated that HGF treatment may not only promote the regeneration of epithelial cells but also lead to tissue repair by phenotypic alteration of M1 macrophages to M2‑like macrophages.

摘要

肝细胞生长因子 (HGF) 在细胞运动、增殖和免疫调节功能中发挥着关键作用。然而,HGF 对巨噬细胞的影响尚不清楚。本研究旨在阐明 HGF 对肠固有层单核细胞(LPMCs)表型改变的影响。使用葡聚糖硫酸钠(DSS)在小鼠模型中诱导结肠炎。随后,从患有慢性结肠炎的小鼠中分离 LPMCs,并测定 LPMCs 中细胞因子编码基因的表达水平。用 HGF 培养从 LPMCs 分离出的 CD11b 阳性巨噬细胞,并通过逆转录-定量聚合酶链反应(RT-qPCR)和流式细胞术评估 M1 或 M2 标志物水平的变化。此外,通过 RT-qPCR 和 ELISA 评估细胞因子水平。HGF 将巨噬细胞的表型从 M1 样转变为 M2 样,这是通过 DSS 诱导结肠炎小鼠中精氨酸酶-1、CD206 和 IL-10 的 mRNA 表达水平增加以及 CD86 和 IL-6 的 mRNA 表达水平降低来确定的。此外,HGF 可以通过对免疫细胞的免疫抑制作用来改善 DSS 诱导的结肠炎。这些发现表明,HGF 治疗不仅可以促进上皮细胞的再生,还可以通过将 M1 巨噬细胞表型改变为 M2 样来导致组织修复。

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