title: Study of Wnt2 secreted by A-549 cells in paracrine activation of β-catenin in co-cultured mesenchymal stem cells.
abstract: The canonical Wnt signal pathway is a key regulator of self-renewal and cell fate determination in various types of stem cells. The total pool of β-catenin consists of two different forms: the signaling form of the protein transmits the Wnt signals from the cell membrane to the target genes, whereas the membrane β-catenin is involved in formation of cell-to-cell contact at cadherin junctions. Earlier we developed an in vitro model of epithelial differentiation of mesenchymal stem cells (MSCs) co-cultured with epithelial A-549 cells. The purpose of the present work was to study the role of Wnt2 secreted by the A-549 cells in paracrine induction of β-catenin in co-cultured MSCs. Using the somatic gene knockdown technique, we obtained A-549 cell cultures with down-regulated WNT2. The MSCs co-cultured with the control A-549 cells displayed an increase in the levels of total cellular and signaling β-catenin and transactivation of a reporter construction containing the Lef/Tcf protein family binding sites. In contrast, β-catenin was not induced in the MSCs co-cultured with the A-549 cells with down-regulated WNT2 expression, but the total protein level was increased. We suggest that Wnt2 secreted by A-549 cells induces in co-cultured MSCs the Wnt/β-catenin signaling pathway, whereas the associated increase in total β-catenin level should be due to another mechanism.
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, St. Petersburg, 194064, Russia. borisvp478@gmail.com.
authors.forename: N S
authors.initials: NS
authors.lastname: Petrov
authors.forename: B V
authors.initials: BV
authors.lastname: Popov
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D019899:Paracrine Communication; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D060449:Wnt Signaling Pathway; D051154:Wnt2 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; D034741:RNA, Small Interfering; C495244:WNT2 protein, human; D051154:Wnt2 Protein; D051176:beta Catenin; D018021:Lithium Chloride