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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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| author | Yuri Inoue Ching-Wei Liao Yuki Tsunakawa I-Lin Tsai Satoru Takahashi Michito Hamada |
| author_facet | Yuri Inoue Ching-Wei Liao Yuki Tsunakawa I-Lin Tsai Satoru Takahashi Michito Hamada |
| author_sort | Yuri Inoue |
| collection | DOAJ |
| description | 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. |
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| spelling | doaj.art-b3704e6477934c6ab86ecc8410db18e02023-12-03T13:49:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012316934610.3390/ijms23169346Macrophage-Specific, <i>Mafb</i>-Deficient Mice Showed Delayed Skin Wound HealingYuri Inoue0Ching-Wei Liao1Yuki Tsunakawa2I-Lin Tsai3Satoru Takahashi4Michito Hamada5Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, JapanDepartment of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, JapanDepartment of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, JapanGlobal Innovation Joint-Degree Program, International Joint Degree Master’s Program, Agro-Biomedical Science in Food and Health, College of Medicine, National Taiwan University (NTU GIP-TRIAD), No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, TaiwanDepartment of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, JapanDepartment of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, JapanMacrophages 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.https://www.mdpi.com/1422-0067/23/16/9346macrophageMAFBwound healingskinArg1CCL12 |
| spellingShingle | Yuri Inoue Ching-Wei Liao Yuki Tsunakawa I-Lin Tsai Satoru Takahashi Michito Hamada Macrophage-Specific, <i>Mafb</i>-Deficient Mice Showed Delayed Skin Wound Healing International Journal of Molecular Sciences macrophage MAFB wound healing skin Arg1 CCL12 |
| title | Macrophage-Specific, <i>Mafb</i>-Deficient Mice Showed Delayed Skin Wound Healing |
| title_full | Macrophage-Specific, <i>Mafb</i>-Deficient Mice Showed Delayed Skin Wound Healing |
| title_fullStr | Macrophage-Specific, <i>Mafb</i>-Deficient Mice Showed Delayed Skin Wound Healing |
| title_full_unstemmed | Macrophage-Specific, <i>Mafb</i>-Deficient Mice Showed Delayed Skin Wound Healing |
| title_short | Macrophage-Specific, <i>Mafb</i>-Deficient Mice Showed Delayed Skin Wound Healing |
| title_sort | macrophage specific i mafb i deficient mice showed delayed skin wound healing |
| topic | macrophage MAFB wound healing skin Arg1 CCL12 |
| url | https://www.mdpi.com/1422-0067/23/16/9346 |
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