# Cell Density-Dependent Suppression of Perlecan and Biglycan Expression by Gold Nanocluster in Vascular Endothelial Cells

## TL;DR

A gold nanocluster suppresses proteoglycan expression in vascular cells, potentially offering new insights into vascular disease treatment.

## Contribution

The study reveals a novel mechanism by which gold nanoclusters modulate proteoglycan synthesis via Arf6 inactivation.

## Key findings

- Au25(SG)18 suppresses perlecan expression by inactivating ADP-ribosylation factor 6 (Arf6).
- Au25(SG)18 reduces biglycan expression in vascular endothelial cells at low cell density.
- Arf6-mediated extracellular transport is critical for vascular homeostasis and a potential therapeutic target.

## Abstract

What are the main findings?
Au25(SG)18, a nanoscale gold cluster with low electrophilicity, accumulates in vascular endothelial cells at low cell density and suppresses perlecan expression by inactivating ADP-ribosylation factor 6 (Arf6).Au25(SG)18 also decreases biglycan expression in vascular endothelial cells at low cell density; however, the underlying mechanisms remain unclear.

Au25(SG)18, a nanoscale gold cluster with low electrophilicity, accumulates in vascular endothelial cells at low cell density and suppresses perlecan expression by inactivating ADP-ribosylation factor 6 (Arf6).

Au25(SG)18 also decreases biglycan expression in vascular endothelial cells at low cell density; however, the underlying mechanisms remain unclear.

What are the implications of the main findings?
This study suggests that organic–inorganic hybrid molecules modulate Arf6-mediated protein transport to the extracellular space, revealing a novel mechanism for proteoglycan synthesis regulation.Arf6-mediated extracellular transport plays a critical role in maintaining vascular homeostasis, serving as a potential target to modulate endothelial function and vascular diseases.

This study suggests that organic–inorganic hybrid molecules modulate Arf6-mediated protein transport to the extracellular space, revealing a novel mechanism for proteoglycan synthesis regulation.

Arf6-mediated extracellular transport plays a critical role in maintaining vascular homeostasis, serving as a potential target to modulate endothelial function and vascular diseases.

Proteoglycans are macromolecules consisting of a core protein and one or more glycosaminoglycan side chains. Proteoglycans synthesized by vascular endothelial cells modulate various functions such as anticoagulant activity and vascular permeability. We previously reported that some heavy metals interfere with proteoglycan expression, and that organic–inorganic hybrid molecules, such as metal complexes and organometallic compounds, serve as useful tools to analyze proteoglycan synthesis mechanisms. However, the effects of metal compounds lacking electrophilicity on proteoglycan synthesis remain unclear. Au25(SG)18, a nanoscale gold cluster consisting of a metal core protected by gold–glutathione complexes, exhibits extremely low intramolecular polarity. In this study, we investigated the effect of Au25(SG)18 on proteoglycan synthesis in vascular endothelial cells. Au25(SG)18 accumulated significantly in vascular endothelial cells at low cell density and suppressed the expression of perlecan, a major heparan sulfate proteoglycan in cells, by inactivating ADP-ribosylation factor 6 (Arf6). Additionally, Au25(SG)18 reduced the expression of biglycan, a small dermatan sulfate proteoglycan, in vascular endothelial cells at low cell density; however, the underlying mechanisms remain unclear. Overall, our findings suggest that organic–inorganic hybrid molecules regulate the activity of Arf6-mediated protein transport to the extracellular space and that perlecan is regulated through this mechanism, highlighting the importance of Arf6-mediated extracellular transport for maintaining vascular homeostasis.