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 - Publisher Copyright:
© 2016 Elsevier Ireland Ltd
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 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.
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 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.
KW - Adrenal gland
KW - Aldosterone
KW - Basic fibroblast growth factor
KW - Beta-catenin
KW - CITED2
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U2 - 10.1016/j.mce.2016.11.015
DO - 10.1016/j.mce.2016.11.015
M3 - Article
C2 - 27889473
AN - SCOPUS:85007389308
SN - 0303-7207
VL - 441
SP - 108
EP - 115
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
ER -