Binding to carboxypeptidase M mediates protective effects of fibrinopeptide Bβ_15-42

Area of Science:

• Biochemistry
• Cell Biology
• Physiology

Background:

• Fibrinolysis generates peptides, including Bβ15-42, known for protective effects in ischemia/reperfusion and sepsis.
• Bβ15-42 mediates beneficial effects in endothelial cells by binding to vascular endothelial-cadherin.

Purpose of the Study:

• To investigate the cell-protective activity of Bβ15-42 in tubular cells.
• To identify the molecular mechanism and receptor involved in Bβ15-42's action on tubular cells.

Main Methods:

• Ligand-receptor capture technology (LRC-TriCEPS) was used to identify tubular cell surface receptors for Bβ15-42.
• Carboxypeptidase M (CBPM) was identified as a binding partner.
• CBPM silencing using siRNA and assessment of Bβ15-42's effect on CBPM activity and bradykinin signaling.

Main Results:

• Bβ15-42 exhibits cell-protective activity in tubular cells through a distinct mechanism.
• Carboxypeptidase M (CBPM) was identified as a novel cell surface receptor for Bβ15-42 on tubular cells.
• Silencing CBPM reduced Bβ15-42's protective effects, and Bβ15-42 inhibited CBPM activity and modulated bradykinin signaling.

Conclusions:

• The cytoprotective benefits of Bβ15-42 extend to epithelial tubular cells.
• Carboxypeptidase M (CBPM) is a key receptor mediating Bβ15-42's protective effects in tubular cells.
• Bβ15-42's mechanism in tubular cells involves CBPM inhibition and modulation of bradykinin signaling, distinct from its endothelial cell actions.