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

Area of Science:

• Endocrinology
• Cell Biology
• Molecular Biology

Background:

• Endothelial cells influence adrenal steroidogenesis by modulating proteins like StAR and SF-1.
• The specific endothelial factors mediating this effect on adrenocortical cells remain unidentified.
• Understanding these interactions is crucial for comprehending adrenal function regulation.

Purpose of the Study:

• To investigate how endothelial cell-derived factors control β-catenin activity.
• To identify the specific mechanism by which these factors impact β-catenin in adrenocortical cells.
• To explore the role of basic fibroblast growth factor (bFGF) in this signaling pathway.

Main Methods:

• Reporter gene assays and Western blotting were used to assess β-catenin activity.
• Endothelial cell-conditioned medium (ECCM) was applied to NCIH295R adrenocortical cells.
• Inhibitors of mitogen-activated protein kinase (U0126) and receptor tyrosine kinase (Su5402) were employed.

Main Results:

• ECCM induced nuclear translocation of β-catenin and increased β-catenin-dependent transcription.
• This effect was mediated by receptor tyrosine kinases (RTKs) responsive to basic fibroblast growth factor (bFGF).
• Adrenocortical cells treated with bFGF showed increased bFGF mRNA, and HUVECs secreted bFGF in a density-dependent manner.

Conclusions:

• Endothelial cells regulate β-catenin activity in adrenocortical cells through the secretion of bFGF.
• This pathway involves RTKs and the mitogen-activated protein kinase signaling cascade.
• bFGF represents a key endothelial-derived factor influencing adrenocortical cell function and potentially steroidogenesis.