Basolateral BMP signaling in polarized epithelial cells

PLoS One. 2013 May 13;8(5):e62659. doi: 10.1371/journal.pone.0062659. Print 2013.

Abstract

Bone morphogenetic proteins (BMPs) regulate various biological processes, mostly mediated by cells of mesenchymal origin. However, the roles of BMPs in epithelial cells are poorly understood. Here, we demonstrate that, in polarized epithelial cells, BMP signals are transmitted from BMP receptor complexes exclusively localized at the basolateral surface of the cell membrane. In addition, basolateral stimulation with BMP increased expression of components of tight junctions and enhanced the transepithelial resistance (TER), counteracting reduction of TER by treatment with TGF-β or an anti-tumor drug. We conclude that BMPs maintain epithelial polarity via intracellular signaling from basolaterally localized BMP receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 4 / genetics*
  • Bone Morphogenetic Protein 4 / metabolism
  • Bone Morphogenetic Protein 4 / pharmacology
  • Bone Morphogenetic Protein 6 / genetics*
  • Bone Morphogenetic Protein 6 / metabolism
  • Bone Morphogenetic Protein 6 / pharmacology
  • Bone Morphogenetic Protein Receptors / genetics*
  • Bone Morphogenetic Protein Receptors / metabolism
  • Cell Line
  • Cell Polarity / drug effects
  • Cisplatin / pharmacology
  • Dogs
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Gene Expression
  • Growth Differentiation Factor 2 / genetics*
  • Growth Differentiation Factor 2 / metabolism
  • Growth Differentiation Factor 2 / pharmacology
  • Mice
  • Myoblasts / cytology
  • Myoblasts / drug effects
  • Myoblasts / metabolism
  • Signal Transduction*
  • Tight Junctions / drug effects
  • Tight Junctions / genetics
  • Tight Junctions / metabolism
  • Transforming Growth Factor beta / pharmacology

Substances

  • Bmp4 protein, mouse
  • Bmp6 protein, mouse
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Protein 6
  • Gdf2 protein, mouse
  • Growth Differentiation Factor 2
  • Transforming Growth Factor beta
  • Bone Morphogenetic Protein Receptors
  • Cisplatin

Grants and funding

This study was supported by KAKENHI (Grants-in-Aid for Scientific Research), the Global Center of Excellence (GCOE) Program (International Research Center for Molecular Science in Tooth and Bone Diseases), and the Core-to-Core program “Cooperative International Framework in TGF-β Family Signaling” from the Japan Society for the Promotion of Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.