Liquiritigenin suppresses the activation of hepatic stellate cells via targeting miR-181b/PTEN axis |
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| Affiliation: | 1. Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China;2. Department of Infectious Diseases, The Second Affiliated Hospital and Yuying Children''s Hospital of Wenzhou Medical University, Wenzhou 325000, China;;3. Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China;4. Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China;1. Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, PR China;2. Department of Children''s internal medicine, The Second Affiliated Hospital & Yuying Children''s hospital of Wenzhou Medical University, Wenzhou 325000, PR China;3. Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, PR China;4. Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, PR China;5. Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, PR China;6. Department of Hepatology, Ningbo Yinzhou Second Hospital, Ningbo 315000, PR China;7. Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, PR China;1. The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;2. Center for Drug Safety Evaluation and Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China |
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| Abstract: | BackgroundLiquiritigenin (LQ), an aglycone of liquiritin in licorice, has demonstrated antioxidant, anti-inflammatory and anti-tumor activities. Previously, LQ was found to inhibit liver fibrosis progression.PurposePhosphatase and tensin homolog (PTEN) has been reported to act as a negative regulator of hepatic stellate cell (HSC) activation. However, the roles of PTEN in the effects of LQ on liver fibrosis have not been identified to date.MethodsThe effects of LQ on liver fibrosis in carbon tetrachloride (CCl4) mice as well as primary HSCs were examined. Moreover, the roles of PTEN and microRNA-181b (miR-181b) in the effects of LQ on liver fibrosis were examined.ResultsLQ markedly ameliorated CCl4-induced liver fibrosis, with a reduction in collagen deposition as well as α-SMA level. Moreover, LQ induced an increase in PTEN and effectively inhibited HSC activation including cell proliferation, α-SMA and collagen expression, which was similar with curcumin (a positive control). Notably, loss of PTEN blocked down the effects of LQ on HSC activation. PTEN was confirmed as a target of miR-181b and miR-181b-mediated PTEN was involved in the effects of LQ on liver fibrosis. LQ led to a significant reduction in miR-181b expression. LQ-inhibited HSC activation could be restored by over-expression of miR-181b. Further studies demonstrated that LQ down-regulated miR-181b level via Sp1. Collectively, we demonstrate that LQ inhibits liver fibrosis, at least in part, via regulation of miR-181b and PTEN.ConclusionLQ down-regulates miR-181b level, leading to the restoration of PTEN expression, which contributes to the suppression of HSC activation. LQ may be a potential candidate drug against liver fibrosis. |
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