MicroRNA-23b-3p regulates human keratinocyte differentiation through repression of TGIF1 and activation of the TGF-ß-SMAD2 signalling pathway.
MicroRNAs (miRNAs) are a class of short non-coding RNAs capable of repressing gene expression at the post-transcriptional level. miRNAs participate in the control of numerous cellular mechanisms, including skin homeostasis and epidermal differentiation. However, few miRNAs involved in these processes have been identified so far in human skin, and the gene networks they control remain largely unknown. Here, we focused on miR-23b-3p, a miRNA that is expressed during the late step of human keratinocyte differentiation. We report that miR-23b-3p silencing modulates epidermal differentiation in human skin reconstructs. The SMAD transcriptional corepressor TGIF1 was identified on bioinformatic analysis as a potential target of miR-23b-3p. Expression analysis and reporter gene assays confirmed direct regulation of TGIF1 expression by miR-23b-3p. Finally, we showed that miR-23-3p was able to activate TGF-ß signalling in human keratinocytes by increasing SMAD2 phosphorylation through TGIF1 repression. Taken together, these data identify miR-23b-3p as a new regulator of human epidermal differentiation in line with TGF-ß signalling.
Université de Lyon, Lyon, France.|Université Lyon 1, Lyon, France.|CNRS, UMR5534, Centre de Génétique et de Physiologie Moléculaires et Cellulaires, Villeurbanne, France.
Laetitia
L
Barbollat-Boutrand
Université de Lyon, Lyon, France.|Université Lyon 1, Lyon, France.|CNRS, UMR5534, Centre de Génétique et de Physiologie Moléculaires et Cellulaires, Villeurbanne, France.
Nicolas
N
Joly-Tonetti
Banque de Tissus et Cellules, Hospices Civiles de Lyon, Lyon, France.
Morgan
M
Dos Santos
Banque de Tissus et Cellules, Hospices Civiles de Lyon, Lyon, France.
Elodie
E
Metral
LabSkin Creations, Lyon, France.
Aurélie
A
Boher
Université de Lyon, Lyon, France.|Université Lyon 1, Lyon, France.|CNRS, UMR5534, Centre de Génétique et de Physiologie Moléculaires et Cellulaires, Villeurbanne, France.
Ingrid
I
Masse
Université de Lyon, Lyon, France.|Université Lyon 1, Lyon, France.|CNRS, UMR5534, Centre de Génétique et de Physiologie Moléculaires et Cellulaires, Villeurbanne, France.
Odile
O
Berthier-Vergnes
INSERM U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
Philippe
P
Bertolino
Banque de Tissus et Cellules, Hospices Civiles de Lyon, Lyon, France.
Odile
O
Damour
Université de Lyon, Lyon, France.|Université Lyon 1, Lyon, France.|CNRS, UMR5534, Centre de Génétique et de Physiologie Moléculaires et Cellulaires, Villeurbanne, France.
Jérôme
J
Lamartine
D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation; D020868:Gene Silencing; D018398:Homeodomain Proteins / Q000235:genetics* / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics*; D010766:Phosphorylation; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics* / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics*; D051899:Smad2 Protein / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D000099222:betaIG-H3 Protein
D016326:Extracellular Matrix Proteins; D018398:Homeodomain Proteins; D035683:MicroRNAs; D017395:Plasminogen Activator Inhibitor 1; D012097:Repressor Proteins; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C552430:MIRN23a microRNA, human; C051321:SERPINE1 protein, human; C497782:SMAD2 protein, human; C097504:TGIF1 protein, human
TGF-beta; differentiation; keratinocytes; microRNA