Format

Send to

Choose Destination
J Invest Dermatol. 2017 Apr;137(4):931-940. doi: 10.1016/j.jid.2016.11.018. Epub 2016 Nov 25.

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

Author information

1
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.
2
Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.
3
Department of Plastic and Reconstructive Surgery, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.
4
Institute of Resource Development and Analysis, Kumamoto University, Honjo, Kumamoto, Japan.
5
Department of Forensic Pathology and Science, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.
6
Schools of Biochemistry and Physiology, Pharmacology and Neuroscience, Faculty of Biomedical Sciences, University of Bristol, University Walk, Bristol, UK.
7
Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan. Electronic address: ryoichi@nagasaki-u.ac.jp.

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.

PMID:
27894934
DOI:
10.1016/j.jid.2016.11.018
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center