Targeting miR‐223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds
Abstract Argonaute 2 bound mature microRNA (Ago2‐miRNA) complexes are key regulators of the wound inflammatory response and function in the translational processing of target mRNAs. In this study, we identified four wound inflammation‐related Ago2‐miRNAs (miR‐139‐5p, miR‐142‐3p, miR‐142‐5p, and miR‐...
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2018-08-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.201809024 |
| _version_ | 1827015141841960960 |
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| author | Maiko de Kerckhove Katsuya Tanaka Takahiro Umehara Momoko Okamoto Sotaro Kanematsu Hiroko Hayashi Hiroki Yano Soushi Nishiura Shiho Tooyama Yutaka Matsubayashi Toshimitsu Komatsu Seongjoon Park Yuka Okada Rina Takahashi Yayoi Kawano Takehisa Hanawa Keisuke Iwasaki Tadashige Nozaki Hidetaka Torigoe Kazuya Ikematsu Yutaka Suzuki Katsumi Tanaka Paul Martin Isao Shimokawa Ryoichi Mori |
| author_facet | Maiko de Kerckhove Katsuya Tanaka Takahiro Umehara Momoko Okamoto Sotaro Kanematsu Hiroko Hayashi Hiroki Yano Soushi Nishiura Shiho Tooyama Yutaka Matsubayashi Toshimitsu Komatsu Seongjoon Park Yuka Okada Rina Takahashi Yayoi Kawano Takehisa Hanawa Keisuke Iwasaki Tadashige Nozaki Hidetaka Torigoe Kazuya Ikematsu Yutaka Suzuki Katsumi Tanaka Paul Martin Isao Shimokawa Ryoichi Mori |
| author_sort | Maiko de Kerckhove |
| collection | DOAJ |
| description | Abstract Argonaute 2 bound mature microRNA (Ago2‐miRNA) complexes are key regulators of the wound inflammatory response and function in the translational processing of target mRNAs. In this study, we identified four wound inflammation‐related Ago2‐miRNAs (miR‐139‐5p, miR‐142‐3p, miR‐142‐5p, and miR‐223) and show that miR‐223 is critical for infection control. miR‐223Y/− mice exhibited delayed sterile healing with prolonged neutrophil activation and interleukin‐6 expression, and markedly improved repair of Staphylococcus aureus‐infected wounds. We also showed that the expression of miR‐223 was regulated by CCAAT/enhancer binding protein alpha in human neutrophils after exposure to S. aureus peptides. Treatment with miR‐223Y/−‐derived neutrophils, or miR‐223 antisense oligodeoxynucleotides in S. aureus‐infected wild‐type wounds markedly improved the healing of these otherwise chronic, slow healing wounds. This study reveals how miR‐223 regulates the bactericidal capacity of neutrophils at wound sites and indicates that targeting miR‐223 might be of therapeutic benefit for infected wounds in the clinic. |
| first_indexed | 2024-03-07T17:38:55Z |
| format | Article |
| id | doaj.art-5d5fcb93f7564cd5a95e07278a823ab0 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2025-02-18T14:18:46Z |
| publishDate | 2018-08-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-5d5fcb93f7564cd5a95e07278a823ab02024-10-28T08:56:42ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842018-08-01101012110.15252/emmm.201809024Targeting miR‐223 in neutrophils enhances the clearance of Staphylococcus aureus in infected woundsMaiko de Kerckhove0Katsuya Tanaka1Takahiro Umehara2Momoko Okamoto3Sotaro Kanematsu4Hiroko Hayashi5Hiroki Yano6Soushi Nishiura7Shiho Tooyama8Yutaka Matsubayashi9Toshimitsu Komatsu10Seongjoon Park11Yuka Okada12Rina Takahashi13Yayoi Kawano14Takehisa Hanawa15Keisuke Iwasaki16Tadashige Nozaki17Hidetaka Torigoe18Kazuya Ikematsu19Yutaka Suzuki20Katsumi Tanaka21Paul Martin22Isao Shimokawa23Ryoichi Mori24Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical SciencesDepartment of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical SciencesDepartment of Forensic Pathology and Science, Nagasaki University School of Medicine and Graduate School of Biomedical SciencesDepartment of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical SciencesLaboratory of Functional Genomics, Department of Medical Genome Science, Graduate of Frontier Science, The University of TokyoDepartment of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical SciencesDepartment of Plastic and Reconstructive Surgery, Nagasaki University School of Medicine and Graduate School of Biomedical SciencesDepartment of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical SciencesDepartment of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical SciencesSchools of Biochemistry and Physiology, Pharmacology & Neuroscience, Faculty of Biomedical Sciences, University of BristolDepartment of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical SciencesDepartment of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical SciencesDepartment of Ophthalmology, Wakayama Medical UniversityFaculty of Pharmaceutical Sciences, Tokyo University of ScienceFaculty of Pharmaceutical Sciences, Tokyo University of ScienceFaculty of Pharmaceutical Sciences, Tokyo University of ScienceDepartment of Pathology, Sasebo City General Hospital, SaseboDepartment of Pharmacology, Faculty of Dentistry, Osaka Dental University, HirakataDepartment of Applied Chemistry, Faculty of Science, Tokyo University of ScienceDepartment of Forensic Pathology and Science, Nagasaki University School of Medicine and Graduate School of Biomedical SciencesLaboratory of Functional Genomics, Department of Medical Genome Science, Graduate of Frontier Science, The University of TokyoDepartment of Plastic and Reconstructive Surgery, Nagasaki University School of Medicine and Graduate School of Biomedical SciencesSchools of Biochemistry and Physiology, Pharmacology & Neuroscience, Faculty of Biomedical Sciences, University of BristolDepartment of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical SciencesDepartment of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical SciencesAbstract Argonaute 2 bound mature microRNA (Ago2‐miRNA) complexes are key regulators of the wound inflammatory response and function in the translational processing of target mRNAs. In this study, we identified four wound inflammation‐related Ago2‐miRNAs (miR‐139‐5p, miR‐142‐3p, miR‐142‐5p, and miR‐223) and show that miR‐223 is critical for infection control. miR‐223Y/− mice exhibited delayed sterile healing with prolonged neutrophil activation and interleukin‐6 expression, and markedly improved repair of Staphylococcus aureus‐infected wounds. We also showed that the expression of miR‐223 was regulated by CCAAT/enhancer binding protein alpha in human neutrophils after exposure to S. aureus peptides. Treatment with miR‐223Y/−‐derived neutrophils, or miR‐223 antisense oligodeoxynucleotides in S. aureus‐infected wild‐type wounds markedly improved the healing of these otherwise chronic, slow healing wounds. This study reveals how miR‐223 regulates the bactericidal capacity of neutrophils at wound sites and indicates that targeting miR‐223 might be of therapeutic benefit for infected wounds in the clinic.https://doi.org/10.15252/emmm.201809024inflammationmiR‐223neutrophilskin wound healingStaphylococcus aureus |
| spellingShingle | Maiko de Kerckhove Katsuya Tanaka Takahiro Umehara Momoko Okamoto Sotaro Kanematsu Hiroko Hayashi Hiroki Yano Soushi Nishiura Shiho Tooyama Yutaka Matsubayashi Toshimitsu Komatsu Seongjoon Park Yuka Okada Rina Takahashi Yayoi Kawano Takehisa Hanawa Keisuke Iwasaki Tadashige Nozaki Hidetaka Torigoe Kazuya Ikematsu Yutaka Suzuki Katsumi Tanaka Paul Martin Isao Shimokawa Ryoichi Mori Targeting miR‐223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds EMBO Molecular Medicine inflammation miR‐223 neutrophil skin wound healing Staphylococcus aureus |
| title | Targeting miR‐223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds |
| title_full | Targeting miR‐223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds |
| title_fullStr | Targeting miR‐223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds |
| title_full_unstemmed | Targeting miR‐223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds |
| title_short | Targeting miR‐223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds |
| title_sort | targeting mir 223 in neutrophils enhances the clearance of staphylococcus aureus in infected wounds |
| topic | inflammation miR‐223 neutrophil skin wound healing Staphylococcus aureus |
| url | https://doi.org/10.15252/emmm.201809024 |
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