Perfluorooctane sulfonate aggravates <scp>CCl4</scp>‐induced hepatic fibrosis via <scp>HMGB1</scp>/<scp>TLR4</scp>/Smad signaling

Wan, Chunhua; Gu, Ting Ting; Ling, Junyi; Qin, Yi; Luo, Jiashan; Sun, Lin; Hua, Lu; Zhao, Jianya; Jiang, Shengyang

doi:10.1002/tox.23458

Cited by 8 publications

(6 citation statements)

References 50 publications

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“…It may be related to changes in lipid and bile acid metabolism ( 9 , 59 ). In animal models, exposure to subchronic PFOS has been found to enhance hepatic stellate cell (HSC) activation and exacerbate carbon tetrachloride (CCl 4 )-induced liver fibrosis ( 60 ), consistent with the outcomes of Sen’s study, which showed that PFOS was positively associated with hepatic fibrosis in adults ( 9 ). In contrast, a study including adults from the C8 Health Project in the USA showed that cumulative PFOA exposure had no effect on all liver diseases, enlarged liver, or cirrhosis ( 58 ).…”

Section: Relationship Between Nafld and Edcssupporting

confidence: 60%

Endocrine disrupting chemicals: A promoter of non-alcoholic fatty liver disease

Chen

Wang

Cui

et al. 2023

Front. Public Health

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Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disorder. With the improvement in human living standards, the prevalence of NAFLD has been increasing in recent years. Endocrine-disrupting chemicals (EDCs) are a class of exogenous chemicals that simulate the effects of hormones in the body. There has been growing evidence regarding the potential effects of EDCs on liver health, especially in NAFLD. This paper aims to summarize the major EDCs that contribute to the growing burden of NAFLD and to raise public awareness regarding the hazards posed by EDCs with the objective of reducing the incidence of NAFLD.

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Section: Relationship Between Nafld and Edcssupporting

confidence: 60%

Endocrine disrupting chemicals: A promoter of non-alcoholic fatty liver disease

Chen

Wang

Cui

et al. 2023

Front. Public Health

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“…Organisms can be exposed to PFOS through ingestion of food and drinking water, breathing air, and exposure to contaminated medium 2 . The use of PFOS has been restricted due to its environmental persistence and biotoxicity 3 . Unfortunately, PFOS is now widely detected in the environment, and continually poses a great threat to the health of organisms 4 .…”

Section: Introductionmentioning

confidence: 99%

“…The use of PFOS has been restricted due to its environmental persistence and biotoxicity. 3 Unfortunately, PFOS is now widely detected in the environment, and continually poses a great threat to the health of organisms. 4 Existing reports have shown that immunosuppression have been observed in the general population exposed to PFOS.…”

mentioning

confidence: 99%

Perfluorooctane sulfonate‐induced apoptosis in kidney cells by triggering the NOX4/ROS/JNK axis and antagonism of cannabidiol

Luo

et al. 2023

Environmental Toxicology

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Perfluorooctane sulfonate (PFOS) is one of the persistent organic pollutants (POPs), which can cause severe nephrotoxicity in mammals. Cannabinol (CBD), a nonpsychoactive cannabinoid obtained from the cannabis plant, has attracted attention in recent years for its excellent antioxidant properties. NADPH oxidase 4 (NOX4) has an important effect in supporting normal renal physiological function. The potential mechanisms of PFOS nephrotoxicity and whether CBD can prevent renal damage caused by PFOS remain unclear. This work aimed to study the mechanisms of PFOS‐induced kidney damage and the protective role of CBD against PFOS‐induced kidney damage. We demonstrated that PFOS led to renal insufficiency and structural damage in mice, induced overexpression of NOX4 and the onset of oxidative stress, and activated apoptosis of the mitochondrial pathway via the JNK signaling pathway. However, treatment with CBD reversed these changes. For further investigation of the potential mechanism of PFOS‐induced renal cell apoptosis, the expression of NOX4 was inhibited in vitro experiments using Apocynin, an effective NOX4 inhibitor. The outcomes showed that PFOS‐induced ROS production and JNK signaling pathway activation and apoptosis in human embryonic kidney (HEK293) cells were significantly reduced after inhibition of NOX4. This suggests that PFOS‐induced NOX4 overexpression serves as an upstream event for JNK pathway activation. In conclusion, the findings suggest that PFOS induces apoptosis in renal cells via the NOX4/ROS/JNK pathway. Meanwhile, CBD alleviated PFOS‐induced renal apoptosis through the inhibition of NOX4/ROS/JNK axis activation.

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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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Perfluorooctane sulfonate aggravates CCl4‐induced hepatic fibrosis via HMGB1/TLR4/Smad signaling

Cited by 8 publications

References 50 publications

Endocrine disrupting chemicals: A promoter of non-alcoholic fatty liver disease

Endocrine disrupting chemicals: A promoter of non-alcoholic fatty liver disease

Perfluorooctane sulfonate‐induced apoptosis in kidney cells by triggering the NOX4/ROS/JNK axis and antagonism of cannabidiol

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

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