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Study of Wnt2 secreted by A-549 cells in paracrine activation of β-catenin in co-cultured mesenchymal stem cells

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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.

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Abbreviations

ABC:

active (signaling) β-catenin

MSCs:

mesenchymal stem cells

TBC:

total β-catenin

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Authors and Affiliations

  1. Institute of Cytology, Russian Academy of Sciences, Tikhoretsky pr. 4, 194064, St. Petersburg, Russia

    N. S. Petrov & B. V. Popov

Authors
  1. N. S. Petrov
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  2. B. V. Popov
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Correspondence to B. V. Popov.

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Original Russian Text © N. S. Petrov, B. V. Popov, 2014, published in Biokhimiya, 2014, Vol. 79, No. 6, pp. 666–674.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM14-045, April 27, 2014.

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Petrov, N.S., Popov, B.V. Study of Wnt2 secreted by A-549 cells in paracrine activation of β-catenin in co-cultured mesenchymal stem cells. Biochemistry Moscow 79, 524–530 (2014). https://doi.org/10.1134/S0006297914060054

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