1. Academic Validation
  2. Berberine inhibits low shear stress-induced glycocalyx degradation via modulating AMPK and p47phox/Hyal2 signal pathway

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

  • Eur J Pharmacol. 2019 Aug 5;856:172413. doi: 10.1016/j.ejphar.2019.172413.
Hongfeng Yang 1 Linlin Zhu 2 Yue Gu 2 Xiangquan Kong 2 Yan Liu 2 Mingxing Chen 3 Xiangrong Xie 2 Jie Luo 2 Shaoliang Chen 4
Affiliations

Affiliations

  • 1 Department of Intensive Care Unit, Affiliated People's Hospital of Jiangsu University, Zhenjiang, China; Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
  • 2 Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
  • 3 Department of Cardiology, Affiliated Hospital of Yangzhou University, Yangzhou, China.
  • 4 Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China. Electronic address: chmengx@126.com.
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 p47phox/hyaluronidase 2 (Hyal2) signaling pathway involved in the modulation of hyaluronic acid metabolism. Further, berberine, by increasing AMPK phosphorylation, decreased the dissociation of p47phox/Hyal2, and subsequently inhibited Hyal2 activation and p47phox phosphorylation, leading to the metabolic maintaining of hyaluronic acid. Importantly, we primarily demonstrated a direct binding between AMPKα and p47phox in HUVECs by co-immunoprecipitation. On the Other hand, berberine also increased the expression of hyaluronic acid synthase 2 (HAS2) by regulating AMPKα/p47phox 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 p47phox and Hyal2 activity but also upregulates the expression of HAS2.

Keywords

Berberine; Hyaluronic acid; Hyaluronic acid synthase 2; Hyaluronidase 2; Low shear stress.

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