Arpin deficiency increases actomyosin contractility and vascular permeability

Area of Science:

• Cell Biology
• Vascular Biology
• Biochemistry

Background:

• Arpin is a known Arp2/3 complex inhibitor involved in cell migration.
• Arpin stabilizes epithelial barriers via Arp2/3-dependent mechanisms.
• The role of arpin in endothelial cells (EC) remained uncharacterized.

Purpose of the Study:

• To investigate the expression and function of arpin in endothelial cells.
• To determine arpin's role in endothelial barrier integrity and actomyosin contractility.
• To elucidate arpin's function in vivo using a mouse model.

Main Methods:

• Arpin expression analysis in EC.
• Arpin depletion using siRNA in Human Umbilical Vein Endothelial Cells (HUVECs).
• Assessment of actin cytoskeleton organization and endothelial permeability.
• Pharmacological inhibition of ROCK1 and ZIPK.
• Phenotypic analysis of arpin-deficient mice, focusing on lung vasculature.

Main Results:

• Arpin mRNA and protein are expressed in EC and downregulated by inflammatory cytokines.
• Arpin depletion in HUVECs induced stress fiber formation and increased permeability independently of Arp2/3.
• ROCK1 and ZIPK inhibition rescued the effects of arpin depletion on actin and permeability.
• Arpin-deficient mice exhibited lung vascular defects, including edema, hemorrhage, and increased permeability.

Conclusions:

• Arpin functions as a regulator of actomyosin contractility and endothelial barrier integrity in EC.
• Arpin's role in EC barrier function is independent of its Arp2/3 inhibitory activity.
• Arpin is crucial for maintaining vascular integrity in vivo.