Dihydroartemisinin inhibits the proliferation of IgAN mesangial cells through the mTOR signaling pathway

Abstract

IgA nephropathy (IgAN) is an autoimmune kidney disease and is the most prevalent form of glomerular kidney disease in China and worldwide. IgA immune complex deposition accompanied by mesangial cell proliferation and mesangial matrix expansion is the most basic pathological feature of IgAN. Dihydroartemisinin (DHA), an antimalarial drug, was recently reported to be effective in treating autoimmune diseases. However, its potential therapeutic role in IgAN is relatively unstudied. The aim of this study was to investigate the pharmacological effects and the underlying mechanisms of DHA in the treatment of IgAN. In this study, renal biopsy specimens were collected for immunohistochemistry. In vitro, 25 μg/ml concentrations of aggregated IgA1 (aIgA1) was used to construct the IgAN mesangial cell model. Stimulated human mesangial cells (HMCs) were treated for 24 h with DHA (0-15 μM) and were collected for western blot analyses. Cell proliferation was assessed by Cell Counting Kit 8 (CCK8) and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. In vitro, our results showed that DHA could downregulate the mammalian target of rapamycin/ribosomal protein S6 kinase beta-1 (mTOR/S6K1) signaling pathway, promote cell autophagy, and ameliorate cell proliferation in aIgA1-induced HMCs. The results suggested that DHA may represent a novel class of mTOR inhibitor and promote an anti-proliferation effect in IgAN HMCs, which provides an alternative approach for IgAN treatment.

Keywords: Dihydroartemisinin; IgA nephropathy; Mesangial cell proliferation; rapamycin/ribosomal protein S6 kinase beta-1 pathway.