Intestinal epithelial β Klotho is a critical protective factor in alcohol-induced intestinal barrier dysfunction and liver injury

Hou, Zhengping; Ding, Qiuying; Li, Yuqi; Zhang, Zhibo; Yan, Fang; Li, Yanping; Wang, Xingxing; Xu, Jingyuan; Chen, Weiting; Wu, Guicheng; Ruan, Xiongzhong; Zhao, Lei

doi:10.1016/j.ebiom.2022.104181

Cited by 13 publications

(13 citation statements)

References 62 publications

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“…The viability of Caco-2 cells exposed to 25 or 50 μM galangin for 24 h did not vary significantly from that of the untreated group (Figure ), indicating no adverse effects on cell viability. Our data and other studies − indicated that galangin significantly decreased ethanol-induced cell death in a dose-depended manner (Figure B,C). To evaluate the impact of galangin on ethanol-induced damage on Caco-2 cell integrity, we analyzed the expression of TJ proteins.…”

Section: Resultssupporting

confidence: 84%

“…In DMEM supplemented with 10% (v/v) fetal bovine serum (Life Technologies, Carlsbad, CA, USA), Caco-2 cells (ATCC; Rockville, MD, USA) were cultured according to normal protocols. For ethanol treatment, 2.5% (v/v) ethanol (429.25 mM) was maintained for 24 h to simulate in vitro intestinal barrier damage. , Caco-2 cells were introduced into a 96-well plate with a seeding density of 1 × 10 4 cells per well, and then after 2h of galangin treatment at a concentration of 25–100 μM, the samples were subjected to ethanol for an additional 24 h.…”

Section: Methodsmentioning

confidence: 99%

“…For ethanol treatment, 2.5% (v/v) ethanol (429.25 mM) was maintained for 24 h to simulate in vitro intestinal barrier damage. 21,22 Caco-2 cells were introduced into a 96-well plate with a seeding density of 1 × 10 4 cells per well, and then after 2h of galangin treatment at a concentration of 25−100 μM, the samples were subjected to ethanol for an additional 24 h.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…In our present study, ethanol ignited a distinct diminish in expression of ZO-1 and occludin, accompanied with decreased immunoreactivity and fluorescence intensity in IHC and IF staining, which is in line with previous studies. 21,32 More importantly, pretreatment with galangin dramatically reversed ethanol-induced downregulation of TJ proteins in both Caco-2 cells and in mouse colons.…”

Section: Galangin Prevents Against Ethanol-activated Phosphorylation ...mentioning

confidence: 98%

“…To confirm this, we treated Caco-2 cells with the P38 inhibitor SB203580 (10 μM), JNK inhibitor SP600125 (10 μM), ERK inhibitor PD98059 (10 Numerous reports have proved that ethanol can induce oxidative damage in the gastrointestinal tract, increase intestinal permeability, and disrupt the balance of the gut microbiota balance, ultimately resulting in endotoxemia inside the organism. 6,21,27 Galangin is considered as a promising flavone for mitigating intestinal injury. Cai et al 24 discovered that galangin exerts a great anti-inflammatory effect against LPSprovoked intestinal epithelial cells.…”

Section: Galangin Prevents Against An Ethanol-induced Decrease Of Int...mentioning

confidence: 99%

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Galangin Prevents Against Ethanol-Induced Intestinal Barrier Dysfunction and NLRP3 Inflammasome Activation via NF-κB/MAPK Signaling Pathways in Mice and Caco-2 Cells

Zhao,

Li,

Liu

et al. 2024

J. Agric. Food Chem.

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The potential of natural phytochemicals in addressing ethanol-related public safety concerns has been garnering attention. Galangin, a potent flavonoid renowned for its antioxidative and anti-inflammatory characteristics, is derived from the galanga plant, and propolis is derived from bees. Here, we documented the effects of galangin on ethanol-stimulated intestinal tight junction damage and investigated its potential protective mechanism in both in vivo and in vitro models, which has not been extensively investigated. Our results revealed that galangin efficaciously mitigated ethanol-induced intestine injury and dysfunction of the intestinal barrier. Concurrently, galangin significantly counteracted the ethanol-induced upregulation of NLRP3 inflammasomeassociated proteins and activated the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways in both the mouse colon and Caco-2 cells. Interestingly, similar to galangin, inhibitors of MAPKs and the NF-κB p65 reduced ethanol-induced NLRP3 inflammasome activation and intestinal tight junction damage. To sum up, our results showed that galangin blocks the ethanol-induced perturbation of the intestinal barrier and activation of the NLRP3 inflammasome via the NF-κB/MAPK signaling pathways.

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Section: Resultssupporting

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Section: ■ Materials and Methodsmentioning

confidence: 99%

Section: Galangin Prevents Against Ethanol-activated Phosphorylation ...mentioning

confidence: 98%

Section: Galangin Prevents Against An Ethanol-induced Decrease Of Int...mentioning

confidence: 99%

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Galangin Prevents Against Ethanol-Induced Intestinal Barrier Dysfunction and NLRP3 Inflammasome Activation via NF-κB/MAPK Signaling Pathways in Mice and Caco-2 Cells

Zhao,

Li,

Liu

et al. 2024

J. Agric. Food Chem.

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Intestinal NSD2 Aggravates Nonalcoholic Steatohepatitis Through Histone Modifications

Zhang,

Qiao,

et al. 2024

Advanced Science

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Mounting clinical evidence suggests that a comprised intestinal barrier contributes to the progression of nonalcoholic steatohepatitis (NASH); nevertheless, the precise mechanism remains elusive. This study unveils a significant upregulation of nuclear receptor‐binding SET domain protein 2 (NSD2) in the intestines of obese humans and mice subjected to a high‐fat cholesterol diet (HFCD). Intestine‐specific NSD2 knockout attenuated the progression of intestinal barrier impairment and NASH, whereas NSD2 overexpression exacerbated this progression. Mechanistically, NSD2 directly regulates the transcriptional activation of Ern1 by demethylating histone H3 at lysine 36 (H3K36me2), thus activating the ERN1–JNK axis to intensify intestinal barrier impairment and subsequently foster NASH progression. These findings elucidate the crucial role of NSD2‐mediated H3K36me2 in intestinal barrier impairment, suggesting that targeting intestinal NSD2 can represent a novel therapeutic approach for NASH.

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β-Klotho as novel therapeutic target in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A narrative review

Meroni,

Dongiovanni,

Tiano

et al. 2024

Biomedicine & Pharmacotherapy

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Intestinal epithelial β Klotho is a critical protective factor in alcohol-induced intestinal barrier dysfunction and liver injury

Cited by 13 publications

References 62 publications

Galangin Prevents Against Ethanol-Induced Intestinal Barrier Dysfunction and NLRP3 Inflammasome Activation via NF-κB/MAPK Signaling Pathways in Mice and Caco-2 Cells

Galangin Prevents Against Ethanol-Induced Intestinal Barrier Dysfunction and NLRP3 Inflammasome Activation via NF-κB/MAPK Signaling Pathways in Mice and Caco-2 Cells

Intestinal NSD2 Aggravates Nonalcoholic Steatohepatitis Through Histone Modifications

β-Klotho as novel therapeutic target in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A narrative review

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