miR-483-3p controls proliferation in wounded epithelial cells. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue FASEB Journal Année : 2011

miR-483-3p controls proliferation in wounded epithelial cells.

Résumé

The mechanisms that regulate keratinocyte migration and proliferation in wound healing remain largely unraveled, notably regarding possible involvements of microRNAs (miRNAs). Here we disclose up-regulation of miR-483-3p in 2 distinct models of wound healing: scratch-injured cultures of human keratinocytes and wounded skin in mice. miR-483-3p accumulation peaks at the final stage of the wound closure process, consistent with a role in the arrest of "healing" progression. Using an in vitro wound-healing model, videomicroscopy, and 5-bromo-2'-uridine incorporation, we observed that overexpression of miR-483-3p inhibits keratinocyte migration and proliferation, whereas delivery of anti-miR-483-3p oligonucleotides sustains keratinocyte proliferation beyond the closure of the wound, compared with irrelevant anti-miR treatment. Expression profiling of keratinocytes transfected with miR-483-3p identified 39 transcripts that were both predicted targets of miR-483-3p and down-regulated after miR-483-3p overexpression. Luciferase reporter assays, Western blot analyses, and silencing by specific siRNAs finally established that kinase MK2, cell proliferation marker MKI67, and transcription factor YAP1 are direct targets of miR-483-3p that control keratinocyte proliferation. miR-483-3p-mediated down-regulation of MK2, MKI67, and YAP1 thus represents a novel mechanism controlling keratinocyte growth arrest at the final steps of reepithelialization.-Bertero, T., Gastaldi, C., Bourget-Ponzio, I., Imbert, V., Loubat, A., Selva, E., Busca, R., Mari, B., Hofman, P., Barbry, P., Meneguzzi, G., Ponzio, G., Rezzonico, R. miR-483-3p controls proliferation in wounded epithelial cells.
Fichier non déposé

Dates et versions

hal-00626120 , version 1 (23-09-2011)

Identifiants

Citer

Thomas Bertero, Cécile Gastaldi, Isabelle Bourget-Ponzio, Véronique Imbert, Agnès Loubat, et al.. miR-483-3p controls proliferation in wounded epithelial cells.. FASEB Journal, 2011, 25 (9), pp.3092-105. ⟨10.1096/fj.10-168401⟩. ⟨hal-00626120⟩
112 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More