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

Fujino,Yusuke; Kanmura,Shuji; Morinaga,Yuko; Kojima,Issei; Maeda,Nobuhisa; Tanaka,Akihito; Maeda,Hidehito; Kumagai,Kotaro; Sasaki,Fumisato; Tanoue,Shiroh; Ido,Akio

doi:10.3892/mmr.2023.12957

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

Authors:
- Yusuke Fujino
- Shuji Kanmura
- Yuko Morinaga
- Issei Kojima
- Nobuhisa Maeda
- Akihito Tanaka
- Hidehito Maeda
- Kotaro Kumagai
- Fumisato Sasaki
- Shiroh Tanoue
- Akio Ido
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Affiliations: 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
Published online on: February 10, 2023 https://doi.org/10.3892/mmr.2023.12957
Article Number: 70
Copyright: © Fujino et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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