title: MiR-142 Is Required for Staphylococcus aureus Clearance at Skin Wound Sites via Small GTPase-Mediated Regulation of the Neutrophil Actin Cytoskeleton.
abstract: MicroRNAs (miRNAs) are small noncoding RNAs that regulate protein translation by binding to complementary target mRNAs. We previously identified two mature members of the miR-142 family, miR-142-5p and miR-142-3p, as inflammation-related miRNAs with potential roles in wound healing. Here, we demonstrated that these two miRNAs are prominently expressed in wound-infiltrated neutrophils and macrophages and play central roles in wound healing. We generated miR-142-/-mice using the exchangeable gene-trap method and showed that healing of Staphylococcus aureus-infected skin wounds was significantly delayed in miR-142-/-mice compared with that in wild-type mice. MiR-142-/-mice exhibited abnormal abscess formation at S. aureus-infected skin wound sites and were also more susceptible to horizontal transmission of wound infections. MiR-142-/-neutrophils showed altered phagocytosis as a consequence of chemotactic behavior, including enhanced F-actin assembly, disturbed cell polarity, and increased cell motility. We showed that these changes were linked to cytoskeletal regulation, and that expression of the small GTPases was markedly increased in miR-142-/-neutrophils. Collectively, our data demonstrate that the miR-142 family is indispensable for protection against S. aureus infection and its clearance at wound sites. MiR-142-3p and miR-142-5p play nonredundant roles in actin cytoskeleton regulation by controlling small GTPase translation in neutrophils at wound sites.
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan; Department of Plastic and Reconstructive Surgery, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Kim
authors.affiliation: Department of Plastic and Reconstructive Surgery, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yano
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.
authors.forename: Gaku
authors.initials: G
authors.lastname: Matsumoto
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.
authors.forename: Ryoma
authors.initials: R
authors.lastname: Ohuchida
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.
authors.forename: Yuhoko
authors.initials: Y
authors.lastname: Ishikura
authors.affiliation: Institute of Resource Development and Analysis, Kumamoto University, Honjo, Kumamoto, Japan.
authors.forename: Masatake
authors.initials: M
authors.lastname: Araki
authors.affiliation: Institute of Resource Development and Analysis, Kumamoto University, Honjo, Kumamoto, Japan.
authors.forename: Kimi
authors.initials: K
authors.lastname: Araki
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.
authors.forename: Seongjoon
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Komatsu
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Forensic Pathology and Science, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Ikematsu
authors.affiliation: Department of Plastic and Reconstructive Surgery, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Plastic and Reconstructive Surgery, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Hirano
authors.affiliation: Schools of Biochemistry and Physiology, Pharmacology and Neuroscience, Faculty of Biomedical Sciences, University of Bristol, University Walk, Bristol, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Martin
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Shimokawa
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan. Electronic address: ryoichi@nagasaki-u.ac.jp.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Mori
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D050296:Microbial Viability / Q000235:genetics; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D011897:Random Allocation; D013207:Staphylococcal Skin Infections / Q000378:metabolism* / Q000473:pathology; D014945:Wound Healing / Q000235:genetics*; D014947:Wounds and Injuries / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology
chemical_list: D035683:MicroRNAs; D020559:Monomeric GTP-Binding Proteins