Macrophage-Specific, <i>Mafb</i>-Deficient Mice Showed Delayed Skin Wound Healing

Macrophages play essential roles throughout the wound repair process. Nevertheless, mechanisms regulating the process are poorly understood. MAFB is specifically expressed in the macrophages in hematopoietic tissue and is vital to homeostatic function. Comparison of the skin wound repair rates in ma...

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Bibliographic Details
Main Authors: Yuri Inoue, Ching-Wei Liao, Yuki Tsunakawa, I-Lin Tsai, Satoru Takahashi, Michito Hamada
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/23/16/9346
Description
Summary:Macrophages play essential roles throughout the wound repair process. Nevertheless, mechanisms regulating the process are poorly understood. MAFB is specifically expressed in the macrophages in hematopoietic tissue and is vital to homeostatic function. Comparison of the skin wound repair rates in macrophage-specific, MAFB-deficient mice (<i>Mafb<sup>f/f</sup></i>::LysM-Cre) and control mice (<i>Mafb<sup>f/f</sup></i>) showed that wound healing was significantly delayed in the former. For wounded GFP knock-in mice with GFP inserts in the <i>Mafb</i> locus, flow cytometry revealed that their GFP-positive cells expressed macrophage markers. Thus, macrophages express <i>Mafb</i> at wound sites. Immunohistochemical (IHC) staining, proteome analysis, and RT-qPCR of the wound tissue showed relative downregulation of <i>Arg1</i>, <i>Ccl12</i>, and <i>Ccl2</i> in <i>Mafb<sup>f/f</sup></i>::LysM-Cre mice. The aforementioned genes were also downregulated in the bone marrow-derived, M2-type macrophages of <i>Mafb<sup>f/f</sup></i>::LysM-Cre mice. Published single-cell RNA-Seq analyses showed that <i>Arg1</i>, <i>Ccl2</i>, <i>Ccl12</i>, and <i>Il-10</i> were expressed in distinct populations of MAFB-expressing cells. Hence, the MAFB-expressing macrophage population is heterogeneous. MAFB plays the vital role of regulating multiple genes implicated in wound healing, which suggests that MAFB is a potential therapeutic target in wound healing.
ISSN:1661-6596
1422-0067