Oxymatrine attenuates arsenic-induced endoplasmic reticulum stress and calcium dyshomeostasis in hepatic stellate cells

Huiqun Wang; Bing Han; Nanlan Wang; Yang Lu; Ting Gao; Zihan Qu; Hongmei Yang; Qin Yang

doi:10.21037/atm-20-5881

Oxymatrine attenuates arsenic-induced endoplasmic reticulum stress and calcium dyshomeostasis in hepatic stellate cells

Ann Transl Med. 2020 Sep;8(18):1171. doi: 10.21037/atm-20-5881.

Authors

Huiqun Wang^{1

2

3}, Bing Han^{1

2}, Nanlan Wang^{1

3}, Yang Lu³, Ting Gao⁴, Zihan Qu³, Hongmei Yang³, Qin Yang^{1

3}

Affiliations

¹ Guizhou Provincial Key Laboratory of Pathogenesis & Drug Research on Common Chronic Diseases, Ministry of Education, Guizhou Medical University, Guiyang, China.
² Department of Pathophysiology, Ministry of Education, Guizhou Medical University, Guiyang, China.
³ Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, China.
⁴ Department of Pathology, the Affiliated Hospital of Guizhou Medical University, Guiyang, China.

Abstract

Background: Oxymatrine is the main bioactive component of Sophora flavescens. It exhibits various biological activities and has been used in various liver diseases, including hepatic fibrosis (HF). Hepatic stellate cells (HSCs) are the primary cell type involved during HF progression. Oxymatrine treatment could suppress the proliferation of HSCs and degrade the extracellular cell matrix (ECM), presumed to be associated with HF. However, the mechanism is still unknown.

Methods: NaAsO₂ induces HF in LX2 cells. Oxymatrine was used to treat NaAsO₂- induced LX2 cells. Then, the LX2 cell proliferation, apoptosis, ECM secretion protein, oxidative stress index, and intracellular calcium concentration were respectively measured. Furthermore, after knocking down GRP78 [endoplasmic reticulum (ER) chaperone BiP] or overexpressing of SERCA2 (ATPase sarcoplasmic/ER Ca²⁺ transporting 2) in NaAsO₂-induced LX2 cells, we detected the changes in ER stress and calcium homeostasis in LX2 cells.

Results: NaAsO₂ exposure promoted apoptosis, increased ECM secretion, produced ER stress, and disrupted calcium homeostasis, which could be attenuated by oxymatrine treatment. Furthermore, knockdown of GRP78 to alleviate ER stress, or overexpression of SERCA2 to restore intracellular calcium homeostasis can inhibit the NaAsO₂ effect.

Conclusions: Oxymatrine treatment could improve calcium homeostasis and attenuate ER stress to reverse NaAsO₂-induced HSC activation and ECM secretion, which are the significant phenotypes of HF. The ER stress and calcium homeostasis may be the therapeutic targets for HF.

Keywords: GRP78; Oxymatrine; SERCA2; calcium homeostasis; endoplasmic reticulum stress (ER stress).