Inhibitory Effect of Chebulic Acid on Alveolar Epithelial to Mesenchymal Transition in Response to Urban Particulate Matter Using Co-treatment and Post-treatment Exposure

Lee, Hee Ra; Pyo, Min Cheol; Chae, Seung A; Hong, Chung Oui; Lee, Kwang Won

doi:10.1248/bpb.b19-00061

Cited by 6 publications

(6 citation statements)

References 34 publications

(41 reference statements)

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“…Our previous studies have demonstrated CA’s anti-oxidant ability and its effectiveness in preventing hepatic fibrosis, lung damage owing to urban particulate matter, and vascular dysfunction [ 11 , 12 , 13 ]. In further agreement with previous studies, we also observed that CA (0.5–2.0 μM) significantly ( p < 0.05) prevented the formation of ROS in INS-1 β-cells.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous studies have demonstrated the effects of chebulic acid (CA, Figure 1), a phenolic compound isolated from the fruit of Terminalia chebula Retz, which exhibits anti-oxidant, anti-fibrotic, anti-inflammatory, and anti-glycative effects [10][11][12]. Recently, we verified the effect of CA on alveolar epithelial damage arising from exposure to urban particle matter [13]. However, the preventive effect of CA with respect to pancreatic β-cell damage remains unknown.…”

Section: Introductionmentioning

confidence: 88%

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Chebulic Acid Prevents Methylglyoxal-Induced Mitochondrial Dysfunction in INS-1 Pancreatic β-Cells

Yoo

Hong

et al. 2020

Antioxidants

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To investigate the anti-diabetic properties of chebulic acid (CA) associated with the prevention of methyl glyoxal (MG)-induced mitochondrial dysfunction in INS-1 pancreatic β-cells, INS-1 cells were pre-treated with CA (0.5, 1.0, and 2.0 μM) for 48 h and then treated with 2 mM MG for 8 h. The effects of CA and MG on INS-1 cells were evaluated using the following: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; glyoxalase 1 (Glo-1) expression via Western blot and enzyme activity assays; Nrf-2, nuclear factor erythroid 2-related factor 2 protein expression via Western blot assay; reactive oxygen species (ROS) production assay; mRNA expression of mitochondrial dysfunction related components (UCP2, uncoupling protein 2; VDAC1, voltage-dependent anion-selective channel-1; cyt c, cytochrome c via quantitative reverse transcriptase-PCR; mitochondrial membrane potential (MMP); adenosine triphosphate (ATP) synthesis; glucose-stimulated insulin secretion (GSIS) assay. The viability of INS-1 cells was maintained upon pre-treating with CA before exposure to MG. CA upregulated Glo-1 protein expression and enzyme activity in INS-1 cells and prevented MG-induced ROS production. Mitochondrial dysfunction was alleviated by CA pretreatment; this occurred via the downregulation of UCP2, VDAC1, and cyt c mRNA expression and the increase of MMP and ATP synthesis. Further, CA pre-treatment promoted the recovery from MG-induced decrease in GSIS. These results indicated that CA could be employed as a therapeutic agent in diabetes due to its ability to prevent MG-induced development of insulin sensitivity and oxidative stress-induced dysfunction of β-cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 88%

Chebulic Acid Prevents Methylglyoxal-Induced Mitochondrial Dysfunction in INS-1 Pancreatic β-Cells

Yoo

Hong

et al. 2020

Antioxidants

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“…However, normal lungs we obtained were largely derived from younger donors. It has been shown that CA inhibits urban particulate matter-induced epithelial-to-mesenchymal transition in a human alveolar epithelial cell line (Lee et al, 2019) and reduces reactive oxygen species production and collagen accumulation in a human hepatic stellate cell line (Koo et al, 2016), suggesting that CA may play a multifaceted role in antifibrotic therapies.…”

Section: Qu Et Almentioning

confidence: 99%

Targeting mechanosensitive MDM4 promotes lung fibrosis resolution in aged mice

Yang

Zhu

et al. 2021

Journal of Experimental Medicine

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Aging is a strong risk factor and an independent prognostic factor for progressive human idiopathic pulmonary fibrosis (IPF). Aged mice develop nonresolving pulmonary fibrosis following lung injury. In this study, we found that mouse double minute 4 homolog (MDM4) is highly expressed in the fibrotic lesions of human IPF and experimental pulmonary fibrosis in aged mice. We identified MDM4 as a matrix stiffness–regulated endogenous inhibitor of p53. Reducing matrix stiffness down-regulates MDM4 expression, resulting in p53 activation in primary lung myofibroblasts isolated from IPF patients. Gain of p53 function activates a gene program that sensitizes lung myofibroblasts to apoptosis and promotes the clearance of apoptotic myofibroblasts by macrophages. Destiffening of the fibrotic lung matrix by targeting nonenzymatic cross-linking or genetic ablation of Mdm4 in lung (myo)fibroblasts activates the Mdm4–p53 pathway and promotes lung fibrosis resolution in aged mice. These findings suggest that mechanosensitive MDM4 is a molecular target with promising therapeutic potential against persistent lung fibrosis associated with aging.

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“…Immunofluorescence staining of LX‐2 cells as performed by Lee, Pyo, Chae, Hong, Lee 20 The cells were incubated with anti‐fibronectin primary antibody (1:500, Santa Cruz Biotechnology, Dallas, TX, USA) at 4°C overnight. After this, it was added to the anti‐mouse Alexa 488 green fluorescent secondary antibody for 2 h. After then, 500 ng/mL of 4′, 6″‐diamidino‐2‐phenylindole (DAPI) stained the nuclei.…”

Section: Methodsmentioning

confidence: 99%

“…Immunofluorescence staining of LX-2 cells as performed by Lee, Pyo, Chae, Hong, Lee 20 The cells were incubated with anti-fibronectin pri-…”

Section: Immunofluorescence Stainingmentioning

confidence: 99%

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

Chae

Pyo

Yoo

et al. 2022

Environmental Toxicology

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Ochratoxin A (OTA) is a mycotoxin generated by Penicillium and Aspergillus species. It is often found in cereals. We hypothesized that OTA exposure induces epithelialmesenchymal transition (EMT), leading to liver fibrosis. In this research, we explored whether the TGF-β receptor I (TGF-β RI)/Smad2/3 signaling pathway is related to EMT-induced hepatic fibrosis. In vitro and in vivo experiments, mRNA and protein expression of liver fibrosis-related markers such as fibronectin, α-smooth muscle actin (α-SMA) and E-cadherin were assessed. The levels of alkaline phosphatase, alanine transaminase, aspartate aminotransferase, and total bilirubin, which are used to assess damage, increased. We also confirmed the increase in mRNA and protein expression of TGF-β RI, Smad2, and Smad3. The expression of liver fibrosis-related markers was decreased by siRNA-mediated silencing of Smad2/3, as well as TGF-RI suppression. Liver cells exposed to OTA showed enhanced TGF-β RI expression on the cell membrane. These results demonstrated that OTA induces hepatic fibrosis through TGF-β RI and Smad2/3 pathways in vitro and in vivo.

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Inhibitory Effect of Chebulic Acid on Alveolar Epithelial to Mesenchymal Transition in Response to Urban Particulate Matter Using Co-treatment and Post-treatment Exposure

Cited by 6 publications

References 34 publications

Chebulic Acid Prevents Methylglyoxal-Induced Mitochondrial Dysfunction in INS-1 Pancreatic β-Cells

Chebulic Acid Prevents Methylglyoxal-Induced Mitochondrial Dysfunction in INS-1 Pancreatic β-Cells

Targeting mechanosensitive MDM4 promotes lung fibrosis resolution in aged mice

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

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