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.