Ochratoxin a induces hepatic fibrosis through <scp>TGF</scp>‐β receptor I/Smad2/3 signaling pathway

Chae, Seung A; Pyo, Min Cheol; Yoo, Hee Joon; Lee, Kwang Won

doi:10.1002/tox.23552

Cited by 9 publications

(11 citation statements)

References 44 publications

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“…Its inactivation could reduce liver inflammation, stellate cell activation and collagen deposition. Ctsb deficiency could down‐regulate the expression of tumor necrosis factor‐α (TNF‐α) and transcription inhibitor actinomycin d, induce mitochondria to release cytochrome c and caspase activation, thereby promoting hepatocyte apoptosis 47–50 . However, most of these observations come from hepatocytes and hepatic stellate cells cultured in vitro.…”

Section: Discussionmentioning

confidence: 99%

Exosome‐derived miR‐142‐5p from liver stem cells improves the progression of liver fibrosis by regulating macrophage polarization through CTSB

Zhao

Jiang

et al. 2023

Environmental Toxicology

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Background This study aims to explore the effect of liver stem cells (LSCs)‐derived exosomes and the miR‐142a‐5p carried by them on the process of fibrosis by regulating macrophages polarization. Methods In this study, CCL4 was used to establish liver fibrosis model. The morphology and purity of exosomes (EVs) were verified by transmission electron microscopy, western blotting (WB) and nanoparticle tracing analysis (NTA). Real‐time quantitative PCR (qRT‐PCR), WB and enzyme‐linked immunoadsorption (ELISA) were used to detect liver fibrosis markers, macrophage polarization markers and liver injury markers. Histopathological assays were used to verify the liver injury morphology in different groups. The cell co‐culture model and liver fibrosis model were constructed to verify the expression of miR‐142a‐5p and ctsb. Results Immunofluorescence of LSCs markers CK‐18, epithelial cell adhesion molecule (EpCam), and AFP showed that these markers were up‐regulated in LSCs. In addition, we evaluated the ability of LSCs to excrete EVs by labeling LSCs‐EVs with PKH67. We found that CCL4 and EVs were simultaneously treated at 50 and 100 μg doses, and both doses of EVs could reduce the degree of liver fibrosis in mice. We tested markers of M1 or M2 macrophage polarization and found that EVs reduced M1 marker expression and promoted M2 marker expression. Further, ELISA was used to detect the secreted factors related to M1 and M2 in tissue lysates, which also verified the above views. Further analysis showed that the expression of miR‐142a‐5p increased significantly with the increase of EVs treatment concentration and time. Further, in vitro and in vivo LSCs‐EVs regulate macrophage polarization through miR‐142a‐5p/ctsb pathway and affect the process of liver fibrosis. Conclusion Our data suggest that EVs‐derived miR‐142‐5p from LSCs improves the progression of liver fibrosis by regulating macrophage polarization through ctsb.

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Section: Discussionmentioning

confidence: 99%

Exosome‐derived miR‐142‐5p from liver stem cells improves the progression of liver fibrosis by regulating macrophage polarization through CTSB

Zhao

Jiang

et al. 2023

Environmental Toxicology

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“…According to Jung et al ethanol extract of Pharbitis nil could ameliorate liver fibrosis by the mediation of the TGF- β 1/Smad2 pathway [ 23 ]. TGF- β is a vital modulator in liver fibrosis [ 24 , 25 ]. Furthermore, the progression of diabetes could lead to liver fibrosis [ 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Xiaotangzhike Pill Attenuates the Progression of Diabetes In Vivo through the Mediation of the Akt/GSK-3β Axis

Yang

Wang

Fan

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Diabetes seriously threatens the health of people. Traditional Chinese medicine has been proven to inhibit the progression of diabetes. Meanwhile, the Xiaotangzhike pill (XTZK) was known to alleviate the symptom of diabetes. Thus, this research decided to investigate the mechanism underlying the impact of XTZK in diabetes remains unexplored. Methods. To assess the impact of XTZK in diabetes, in vivo model of diabetes was constructed. The contents of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) in the rats were tested by the commercial kits. In addition, Masson and hematoxylin and eosin (H&E) staining were applied for assessing the histological changes and fibrosis in the rats, respectively. Furthermore, a western blot was applied to assess the protein levels. Results. Streptozotocin (STZ) significantly increased the levels of area under the curve (AUC), TG, TC, LDL-C, and decreased the contents of HDL-C in rats, while these phenomena were partially reversed by XTZK. In addition, STZ notably induced inflammatory infiltration and fibrosis in the liver tissues of rats, which was greatly restored by XTZK. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) in the serum of rats were notably upregulated by STZ, while the effect of STZ was markedly abolished by XTZK. Meanwhile, STZ-caused the upregulation of p-Smad2 and α-SMA in rats was restored by XTZK. Furthermore, XTZK notably inhibited the progression of Qi and Yin deficiency syndrome in diabetes through the mediation of the Akt/GSK-3β axis. Conclusion. The Xiaotangzhike pill attenuates the progression of diabetes through the mediation of the Akt/GSK-3β axis. Hence, our study might supply a novel insight into discovering new strategies against diabetes.

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“…Inflammatory responses have been reported to play an important role in the pathogenesis of HF. Hepatic stellate cell (HSC) activation and interactions between innate and adaptive immune cells play an important role in the progression of fibrosis 5–8 . Therefore, in‐depth exploration of the interaction between immune cells and HSCs plays a role in promoting the mechanism of hepatic fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Autophagy affects hepatic fibrosis progression by regulating macrophage polarization and exosome secretion

Chen

Yan

et al. 2023

Environmental Toxicology

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Background: In this study, the role of autophagy in hepatic fibrosis and its effects on macrophage polarization and exosomes (EVs) were verified by establishing hepatic fibrosis model and co-culture model, providing evidence for treatment. Methods: In this study, CCL 4 was used to establish hepatic fibrosis model. The morphology and purity of exosomes (EVs) were verified by transmission electron microscopy, western blotting (WB), and nanoparticle tracing analysis (NTA). Real-time quantitative PCR (qRT-PCR), WB and enzyme-linked immunoadsorption (ELISA) were used to detect hepatic fibrosis markers, macrophage polarization markers and liver injury markers. Histopathological assays were used to verify the liver injury morphology in different groups. The cell co-culture model and hepatic fibrosis model were constructed to verify the expression of miR-423-5p.Results: Hepatic fibrosis model showed that CCL 4 promoted early autophagy increase but inhibited autophagy flux in liver. mRFP-GFP-LC3 detection showed that both LPS group and Baf group inhibited autophagy flux. This inhibitory effect was reversed by Rap combination therapy. The M1/M2 markers of macrophage polarization were further tested, and it was found that LPS and Baf could promote M1 polarization and inhibit M2 polarization. Rap processing reverses this phenomenon. These data suggest that autophagy can regulate the polarization process of liver macrophages. WB and NTA showed that LPS induced EVs generation. In addition, LPSinduced EVs could promote HSC proliferation, cell cycle, migration, and the expression of fibrosis markers. Macrophage-EVs could affect the fibrosis process of stellate cells through the secretion of miR-423a-5p expression. The hepatic fibrosis model Shengning Zhang and Li Li have contributed equally to this work.

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Ochratoxin a induces hepatic fibrosis through TGF‐β receptor I/Smad2/3 signaling pathway

Cited by 9 publications

References 44 publications

Exosome‐derived miR‐142‐5p from liver stem cells improves the progression of liver fibrosis by regulating macrophage polarization through CTSB

Exosome‐derived miR‐142‐5p from liver stem cells improves the progression of liver fibrosis by regulating macrophage polarization through CTSB

Xiaotangzhike Pill Attenuates the Progression of Diabetes In Vivo through the Mediation of the Akt/GSK-3β Axis

Autophagy affects hepatic fibrosis progression by regulating macrophage polarization and exosome secretion

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