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MiR-142 Is Required for Staphylococcus aureus Clearance at Skin Wound Sites via Small GTPase-Mediated Regulation of the Neutrophil Actin Cytoskeleton

Research output: Contribution to journalArticle

  • Katsuya Tanaka
  • Sang Eun Kim
  • Hiroki Yano
  • Gaku Matsumoto
  • Ryoma Ohuchida
  • Yuhoko Ishikura
  • Masatake Araki
  • Kimi Araki
  • Seongjoon Park
  • Toshimitsu Komatsu
  • Hiroko Hayashi
  • Kazuya Ikematsu
  • Katsumi Tanaka
  • Akiyoshi Hirano
  • Paul Martin
  • Isao Shimokawa
  • Ryoichi Mori
Original languageEnglish
Pages (from-to)931–940
Number of pages10
JournalJournal of Investigative Dermatology
Volume137
Issue number4
Early online date25 Nov 2016
DOIs
DateAccepted/In press - 16 Nov 2016
DateE-pub ahead of print - 25 Nov 2016
DatePublished (current) - Apr 2017

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.

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    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Elsevier at http://www.sciencedirect.com/science/article/pii/S0022202X16326641. Please refer to any applicable terms of use of the publisher.

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    Licence: CC BY-NC-ND

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