Work

Berberine inhibits low shear stress-induced glycocalyx degradation via modulating AMPK and p47phox/Hyal2 signal pathway

Year: 2019

Type: article

Abstract: A characteristic of endothelia damage and repair is the turnover of extracellular matrix components. As a part of extracellular matrix glycosaminoglycan (GAG), hyaluronic acid (HA, main component of glycocalyx) is not only involved in inflammation, proliferation, differentiation of cells, and tissue remodeling, but also functions as a barrier of endothelium via preventing blood flow-induced injury from endothelial layer. Therefore, the metabolism of hyaluronic acid could allow the fine-tuning of cell behavior. In this study, we found that low shear stress decreased the expression of hyaluronic acid , whereas pretreatment with berberine could significantly increase the expression of hyaluronic acid in vitro and in vivo . On this background, it is very important to better understand the beneficial effect of berberine (BBR) on low shear stress-induced degradation of hyaluronic acid and its potential mechanism. By using siRNA and inhibitors, we testified that AMP-activated protein kinase (AMPK) and p47 phox /hyaluronidase 2 (Hyal2) signaling pathway involved in the modulation of hyaluronic acid metabolism. Further, berberine, by increasing AMPK phosphorylation, decreased the dissociation of p47 phox /Hyal2, and subsequently inhibited Hyal2 activation and p47 phox phosphorylation, leading to the metabolic maintaining of hyaluronic acid. Importantly, we primarily demonstrated a direct binding between AMPKα and p47 phox in HUVECs by co-immunoprecipitation. On the other hand, berberine also increased the expression of hyaluronic acid synthase 2 (HAS2) by regulating AMPKα/p47 phox signaling pathway. Taken together, berberine treatment can attenuate low shear stress-induced hyaluronic acid degradation via increasing phosphorylation of AMPKa, and then not only downregulates p47 phox and Hyal2 activity but also upregulates the expression of HAS2.

Source: European Journal of Pharmacology

DOI: 10.1016/j.ejphar.2019.172413