Methyl helicterte ameliorates liver fibrosis by regulating miR-21-mediated ERK and TGF-β1/Smads pathways

Huang, Quanfang; Zhang, Xiaolin; Bai, Facheng; Nie, Jinlan; Song, Wen; Wei, Yuansong; Wei, Jinbin; Huang, Renbin; He, Miao; Lu, Zhaojun; Lin, Xiaobo

doi:10.1016/j.intimp.2018.11.006

Cited by 23 publications

(22 citation statements)

References 26 publications

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“…It was revealed that depleted miR-21 meaningfully decreased cell viability of kidney cancer cells [36]. A study reported that miR-21 down-regulation inactivated TGF-β1 in liver fibrosis [37]. Moreover, it was indicated in our study that restoring PEG3 had the same effect of depleting miR-21 on glioma.…”

Section: Discussionsupporting

confidence: 58%

M2 bone marrow-derived macrophage-derived exosomes shuffle microRNA-21 to accelerate immune escape of glioma by modulating PEG3

Yang

Wang

et al. 2020

Cancer Cell Int

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Background: Growing studies have focused on the role of microRNA-21 (miR-21) in glioma, thus our objective was to discuss the effect of M2 bone marrow-derived macrophage (BMDM)-derived exosomes (BMDM-Exos) shuffle miR-21 on biological functions of glioma cells by regulating paternally expressed gene 3 (PEG3). Methods: Seventy-one cases of human glioma tissues and 30 cases of non-tumor normal brain tissues were collected and stored in liquid nitrogen. PEG3 and miR-21 expression in glioma tissues was tested. The fasting venous blood of glioma patients and healthy control was collected and centrifuged, and then the supernatant was stored at − 80 °C refrigerator. The contents of interferon (IFN)-γ and transforming growth factor-β1 (TGF-β1) in serum were tested by ELISA. Glioma cells and normal glial cells were cultured to screen the target cells for further in vitro experiments. BMDM-Exos was obtained by ultra-high speed centrifugation and then was identified. BMDM-Exos was cocultured with U87 cells to detect the biological functions. The fasting venous blood of glioma patients was extracted and treated with ethylene diamine tetraacetic acid-K2 anti-freezing, and then CD8 + T cells were isolated. CD8 + T cells were co-cultured with U87 cells to detect the CD8 + T proliferation, cell cytotoxic activity, U87 cell activity, as well as IFN-γ and TGF-β1 levels. Moreover, BALB/c-nu/nu mice was taken, and the human-nude mouse glioma orthotopic transplantation model was established with U87 cells, and then mice were grouped to test the trends in tumor growth. The brain of mice (fixed by 10% formaldehyde) was sliced to detect the expression of Ki67 and proliferating cell nuclear antigen (PCNA). The spleen of mice was taken to prepare single-cell suspension, and the percentage of T lymphocytes in spleen to CD8 + T cells was detected. Results: PEG3 expression was decreased and miR-21 expression was increased in glioma cells and tissues. Depleting miR-21 or restoring PEG3 suppressed growth, migration and invasion as well as accelerated apoptosis of glioma cells, also raised CD8 + T proliferation, cell cytotoxic activity, and IFN-γ level as well as decreased U87 cell activity and TGF-β1 level. BMDM-Exos shuttle miR-21 promoted migration, proliferation and invasion as well as suppressed apoptosis of glioma cells by reducing PEG3. Exosomes enhanced the volume of tumor, Ki67 and PCNA expression, reduced the percentage of CD8 + T cells in glioma mice.

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Section: Discussionsupporting

confidence: 58%

M2 bone marrow-derived macrophage-derived exosomes shuffle microRNA-21 to accelerate immune escape of glioma by modulating PEG3

Yang

Wang

et al. 2020

Cancer Cell Int

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“…In this study, porcine serum-induced hepatic fibrotic model rats were built successfully after 12 weeks treatment. e PS-induced rat model is characterized by minor hepatocyte damage but intense immune response, and the mechanisms of fibrogenesis are similar to those of hepatic diseases in humans, especially viral hepatitis, which is one of the main causes of liver fibrosis in China [22,[35][36][37][38]. Our results indicate that liver fibrosis significantly altered the PK of taxifolin in vivo after oral administration of the FPO extract.…”

Section: Discussionsupporting

confidence: 51%

Comparative Pharmacokinetic Study of Taxifolin after Oral Administration of Fructus Polygoni Orientalis Extract in Normal and Fibrotic Rats by UPLC-MS/MS

Wei

Chen

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Fructus polygoni orientalis (FPO) is widely used in clinical practice in China, especially in treatment of liver diseases including viral hepatitis, liver fibrosis, and liver cirrhosis. However, its pharmacokinetic (PK) alterations in liver fibrotic rats have rarely been reported. To study whether taxifolin, one of the main flavonoids in FPO can be absorbed into blood after oral administration of FPO extract and to compare the differences in pharmacokinetic parameters of taxifolin to normal and liver fibrotic rats induced by porcine serum (PS), a UPLC-MS/MS method was developed and validated for determination of taxifolin in rat plasma using puerarin as the internal standard (IS). All validation parameters met the acceptance criteria according to regulatory guidelines. The results indicated that after treatment of rats with PS alone for 12 weeks, the liver fibrotic model group was built successfully. The taxifolin can be absorbed into the blood after oral administration of the FPO extract. The Cmax of taxifolin was 1940 ± 502.2 ng/mL and 2648 ± 208.5 ng/mL (p<0.05), the AUC0∼t of taxifolin was 4949.7 ± 764.89 h·ng/mL and 6679.9 ± 734.26 h·ng/mL (p<0.05), the AUC0∼∞ of taxifolin was 5049.4 ± 760.7 and 7095.2 ± 962.3 h·ng/mL (p<0.05), and the mean residence time (MRT) of taxifolin was 2.46 ± 0.412 h and 3.17 ± 0.039 h (p<0.05) in the normal and fibrotic model groups, respectively. These results confirmed that the pharmacokinetic parameters of taxifolin are altered in liver fibrosis, manifested as Cmax, AUC0∼t, AUC0∼∞, and the mean residence time (MRT). It suggested that it is essential to consider the characteristics of pharmacokinetics after oral administration of FPO in liver disease patients.

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“…Recent studies have defined hepatocyte-derived miR-21 as one of the main driving forces for the progression of hepatic damage into fibrosis as it indirectly activates HSC for ECM synthesis via activation of TGF-β1/Smads, ERK, PTEN/Akt, and NF-κB signaling pathways [52,53]. In addition, serum miR-21 has been reported to be prevalently upregulated during pathogenesis and progression of liver fibrosis in human and mouse models [54].…”

Section: Discussionmentioning

confidence: 99%

Clinical Characteristics, Serum Biochemical Changes, and Expression Profile of Serum Cfa-miRNAs in Dogs Confirmed to Have Congenital Portosystemic Shunts Accompanied by Liver Pathologies

El-Sebaey

Abramov

Abdelhamid

2020

Veterinary Sciences

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Computed tomography angiography (CTA) and biochemical parameters cannot specify liver pathologies in dogs with congenital portosystemic shunts (CPSS) that are easily determined by invasive histopathology. This study aims to assess the possibility of using circulating serum canine familiaris (cfa) microRNAs (miRNAs) as novel non-invasive serum-based fingerprints for liver injuries associated with various morphologies of extrahepatic and intrahepatic portosystemic shunts (EHPSS and IHPSS). Data were obtained from 12 healthy dogs and 84 dogs confirmed to have EHPSS (splenocaval, splenophrenic, splenoazygos, right gastrocaval (RGC), right gastrocaval with caudal loop (RGC–CL)) and IHPSS (right divisional and left divisional) using CTA. Hepatic pathologies were determined by histopathology. Serum expression of miRNAs was assessed by real-time polymerase chain reaction. Based on the nature of liver injuries in each shunt type, cfa-miR-122 was significantly upregulated in all CPSS groups. Meanwhile, serums cfa-miR-34a and 21 were not significantly expressed in splenophrenic or splenoazygos groups, but they were extensively upregulated in splenocaval, RGC, RGC–CL groups and less frequently in right or left divisional groups. Also, serum cfa-miR126 was significantly upregulated in both IHPSS groups but less significantly expressed in RGC, RGC–CL, and splenocaval groups. Overall, estimated cfa-miRNAs could serve as novel biomarkers to mirror the histopathological and molecular events within the liver in each shunt type.

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Methyl helicterte ameliorates liver fibrosis by regulating miR-21-mediated ERK and TGF-β1/Smads pathways

Cited by 23 publications

References 26 publications

M2 bone marrow-derived macrophage-derived exosomes shuffle microRNA-21 to accelerate immune escape of glioma by modulating PEG3

M2 bone marrow-derived macrophage-derived exosomes shuffle microRNA-21 to accelerate immune escape of glioma by modulating PEG3

Comparative Pharmacokinetic Study of Taxifolin after Oral Administration of Fructus Polygoni Orientalis Extract in Normal and Fibrotic Rats by UPLC-MS/MS

Clinical Characteristics, Serum Biochemical Changes, and Expression Profile of Serum Cfa-miRNAs in Dogs Confirmed to Have Congenital Portosystemic Shunts Accompanied by Liver Pathologies

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