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

TY - JOUR

T1 - Endothelial cells regulate β-catenin activity in adrenocortical cells via secretion of basic fibroblast growth factor

AU - Schwafertz, Carolin

AU - Schinner, Sven

AU - Kühn, Markus C

AU - Haase, Matthias

AU - Asmus, Amelie

AU - Mülders-Opgenoorth, Birgit

AU - Ansurudeen, Ishrath

AU - Hornsby, Peter J

AU - Morawietz, Henning

AU - Oetjen, Elke

AU - Schott, Matthias

AU - Willenberg, Holger S

N1 - Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

PY - 2017/2/5

Y1 - 2017/2/5

N2 - 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 NCIH295R 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.

AB - 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 NCIH295R 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.

U2 - 10.1016/j.mce.2016.11.015

DO - 10.1016/j.mce.2016.11.015

M3 - SCORING: Journal article

C2 - 27889473

VL - 441

SP - 108

EP - 115

JO - MOL CELL ENDOCRINOL

JF - MOL CELL ENDOCRINOL

SN - 0303-7207

ER -