TY - JOUR
T1 - MiR-142 Is Required for Staphylococcus aureus Clearance at Skin Wound Sites via Small GTPase-Mediated Regulation of the Neutrophil Actin Cytoskeleton
AU - Tanaka, Katsuya
AU - Kim, Sang Eun
AU - Yano, Hiroki
AU - Matsumoto, Gaku
AU - Ohuchida, Ryoma
AU - Ishikura, Yuhoko
AU - Araki, Masatake
AU - Araki, Kimi
AU - Park, Seongjoon
AU - Komatsu, Toshimitsu
AU - Hayashi, Hiroko
AU - Ikematsu, Kazuya
AU - Tanaka, Katsumi
AU - Hirano, Akiyoshi
AU - Martin, Paul
AU - Shimokawa, Isao
AU - Mori, Ryoichi
PY - 2017/4
Y1 - 2017/4
N2 - 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.
AB - 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.
U2 - 10.1016/j.jid.2016.11.018
DO - 10.1016/j.jid.2016.11.018
M3 - Article (Academic Journal)
C2 - 27894934
SN - 0022-202X
VL - 137
SP - 931
EP - 940
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 4
ER -