Recombinant BMP9 Reinforces Gut Vascular Barrier in Experimental Colitis

Area of Science:

• Gastroenterology
• Vascular Biology
• Immunology

Background:

• Refractory ulcerative colitis (rUC) presents significant treatment challenges.
• Gut vascular barrier (GVB) dysfunction is implicated in persistent rUC.
• The BMP9-ALK1 signaling axis, previously unstudied in UC, was investigated for its role in GVB and treatment resistance.

Purpose of the Study:

• To investigate the association between BMP9-ALK1 signaling dysregulation, GVB impairment, and treatment resistance in ulcerative colitis (UC).
• To explore the therapeutic potential of BMP9 in experimental colitis.

Main Methods:

• Compared serum BMP9 and mucosal ALK1 levels in rUC, non-rUC, and healthy individuals.
• Evaluated BMP9 efficacy in DSS-induced murine colitis (vascular permeability, histopathology, inflammatory markers).
• Investigated mechanistic roles using human intestinal microvascular endothelial cells.

Main Results:

• Serum BMP9 levels were significantly lower in rUC patients and correlated with increased disease severity.
• BMP9 deficiency was linked to treatment-refractory status, independent of baseline severity.
• BMP9 treatment in murine colitis reduced disease severity, inflammation, and vascular leakage by restoring endothelial integrity via ALK1 signaling.

Conclusions:

• Dysregulated BMP9-ALK1 signaling contributes to GVB dysfunction in UC.
• BMP9 supplementation demonstrates therapeutic potential by mitigating vascular leakage and inflammation in experimental colitis.
• The BMP9-ALK1 pathway represents a potential therapeutic target for rUC.