Endothelial cells regulate β-catenin activity in adrenocortical cells via secretion of basic fibroblast growth factor

Carolin Schwafertz, Sven Schinner, Markus C. Kühn, Matthias Haase, Amelie Asmus, Birgit Mülders-Opgenoorth, Ishrath Ansurudeen, Peter J. Hornsby, Henning Morawietz, Elke Oetjen, Matthias Schott, Holger S. Willenberg

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Endothelial cell-derived products influence the synthesis of aldosterone and cortisol in human adrenocortical cells by modulating proteins such as steroidogenic acute-regulatory (StAR) protein, steroidogenic factor (SF)-1 and CITED2. However, the potential endothelial cell-derived factors that mediate this effect are still unknown. The current study was perfomed to look into the control of β-catenin activity by endothelial cell-derived factors and to identify a mechanism by which they affect β-catenin activity in adrenocortical NCI[sbnd]H295R cells. Using reporter gene assays and Western blotting, we found that endothelial cell-conditioned medium (ECCM) led to nuclear translocation of β-catenin and an increase in β-catenin-dependent transcription that could be blocked by U0126, an inhibitor of the mitogen-activated protein kinase pathway. Furthermore, we found that a receptor tyrosin kinase (RTK) was involved in ECCM-induced β-catenin-dependent transcription. Through selective inhibition of RTK using Su5402, it was shown that receptors responding to basic fibroblast growth factor (bFGF) mediate the action of ECCM. Adrenocortical cells treated with bFGF showed a significant greater level of bFGF mRNA. In addition, HUVECs secrete bFGF in a density-dependent manner. In conclusion, the data suggest that endothelial cells regulate β-catenin activity in adrenocortical cells also via secretion of basic fibroblast growth factor.

Original languageEnglish (US)
Pages (from-to)108-115
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume441
DOIs
StatePublished - Feb 5 2017

Keywords

  • Adrenal gland
  • Aldosterone
  • Basic fibroblast growth factor
  • Beta-catenin
  • CITED2

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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