title: miR-142-3p balances proliferation and differentiation of mesenchymal cells during lung development.
abstract: The regulation of the balance between proliferation and differentiation in the mesenchymal compartment of the lung is largely uncharacterized, unlike its epithelial counterpart. In this study, we determined that miR-142-3p contributes to the proper proliferation of mesenchymal progenitors by controlling the level of WNT signaling. miR-142-3p can physically bind to adenomatous polyposis coli mRNA, functioning to regulate its expression level. In miR-142-3p loss-of-function experiments, proliferation of parabronchial smooth muscle cell progenitors is significantly impaired, leading to premature differentiation. Activation of WNT signaling in the mesenchyme, or Apc loss of function, can both rescue miR-142-3p knockdown. These findings show that in the embryonic lung mesenchyme, the microRNA machinery modulates the level of WNT signaling, adding an extra layer of control in the feedback loop between FGFR2C and β-catenin-mediated WNT signaling.
authors.affiliation: University of Giessen Lung Center, Excellence Cluster in Cardio-Pulmonary Systems, member of the German Lung Center (DZL), Department of Internal Medicine II, Aulweg 130, 35392 Giessen, Germany.
authors.forename: Gianni
authors.initials: G
authors.lastname: Carraro
authors.forename: Amit
authors.initials: A
authors.lastname: Shrestha
authors.forename: Jana
authors.initials: J
authors.lastname: Rostkovius
authors.forename: Adriana
authors.initials: A
authors.lastname: Contreras
authors.forename: Cho-Ming
authors.initials: CM
authors.lastname: Chao
authors.forename: Elie
authors.initials: E
authors.lastname: El Agha
authors.forename: Breanne
authors.initials: B
authors.lastname: Mackenzie
authors.forename: Salma
authors.initials: S
authors.lastname: Dilai
authors.forename: Diego
authors.initials: D
authors.lastname: Guidolin
authors.forename: Makoto Mark
authors.initials: MM
authors.lastname: Taketo
authors.forename: Andreas
authors.initials: A
authors.lastname: Günther
authors.forename: Maya E
authors.initials: ME
authors.lastname: Kumar
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.forename: Stijn
authors.initials: S
authors.lastname: De Langhe
authors.forename: Guillermo
authors.initials: G
authors.lastname: Barreto
authors.forename: Saverio
authors.initials: S
authors.lastname: Bellusci
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D017491:Genes, APC; D008168:Lung / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D025601:Adenomatous Polyposis Coli Protein; C495267:CTNNB1 protein, mouse; D035683:MicroRNAs; C532884:MIRN143 microRNA, mouse; D051176:beta Catenin; C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2
keywords: Mesenchymal cell; WNT signaling; miRNA