The decreased expression of integrin αv is involved in T-2 toxin-induced extracellular matrix degradation in chondrocytes

Wang, Hui; Zhang, Meng; Zhang, Ying; Liu, Yinan; Wang, Mengying; Liu, Yue; Liao, Yu−Cheng; Li, Zhengzheng; Feng, Ying; Chen, Jinghong

doi:10.1016/j.toxicon.2021.06.006

Cited by 6 publications

(2 citation statements)

References 30 publications

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“…T-2 toxin was dissolved in absolute ethanol to a concentration of 5 mg/mL and then diluted with PBS. According our previous studies, 22,23 we selected 0, 6, 12, and 24 ng/mL of T-2 toxin, which reduced C28/I2 chondrocytes viability by 10%, 25%, and 50% for subsequent experiments.…”

Section: Cell Viability Assaymentioning

confidence: 99%

T-2 toxin induces articular cartilage damage by increasing the expression of MMP-13 via the TGF-β receptor pathway

Zhang

et al. 2022

Hum Exp Toxicol

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T-2 toxin pre-disposes individuals to osteoarthritis, Kashin–Beck disease (KBD). The major pathological change associated with KBD is the degradation of the articular cartilage matrix. Herein, we investigated the key molecules that regulate T-2 toxin-mediated cartilage degradation. Potential KBD treatments were also investigated. Sprague Dawley rats were divided into the T-2 toxin group and the control group. The T-2 toxin group received 100 ng/g BW/day, whereas the control group received a similar dose of PBS. The expression of matrix metalloproteinase-13 (MMP-13) and TGF-β receptor I/II (TGF-βRI/II) was analyzed using immunohistochemical staining. C28/I2 chondrocytes were exposed to TGF-βRI/II binding inhibitor (GW788388) for 24 h before incubation in different T-2 toxin concentrations (0, 6, 12, and 24 ng/mL for 72 h). The expression of mRNA for TGF-βRI/II, MMP-13 and proteins for MMP-13, and Smad-2 in chondrocytes were analyzed using RT-PCR and western blot, respectively. Safranin O staining revealed that T-2 toxin treatment modulated the expression of articular cartilage matrix. On the other hand, T-2 toxin treatment sharply increased the expression of MMP-13, TGF-βRI, and TGF-βRII in the rat cartilages. Interestingly, blocking the TGF-βRs-smad 2 signaling pathway using GW788388 abrogated the effect of T-2 toxin on upregulating MMP-13 expression. The expression of MMP-13 in chondrocytes induced with T-2 toxin is regulated via the TGF-βRs signaling pathway. As such, inhibiting the expression of TGF-βRs is a potential KBD treatment.

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Section: Cell Viability Assaymentioning

confidence: 99%

T-2 toxin induces articular cartilage damage by increasing the expression of MMP-13 via the TGF-β receptor pathway

Zhang

et al. 2022

Hum Exp Toxicol

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“…In this Sprague-Dawley rat model, epiphyseal plates exhibited chondrocyte necrosis, which is one of the most typical phenotypes for KBD ( 12 ). In addition, numerous in vitro studies uncovered that T-2 toxin-induced chondrocyte injury by regulating the expression levels of Wnt/β-catenin pathway ( 15 , 16 ), SECISBP2-mediated selenoprotein ( 17 ), IGFBP2 ( 18 ), heat shock protein 47 ( 19 ), and integrin α2 ( 20 ), involving in the pathogenesis of KBD. The potential mechanisms are involved in mitochondrial injury, apoptosis, oxidative stress, extracellular matrix metabolic disorders, such as the abnormal expression of MMPs/TIMP-1, type II collagen, and core proteoglycan.…”

Section: Introductionmentioning

confidence: 99%

Fluorine impairs carboxylesterase 1-mediated hydrolysis of T-2 toxin and increases its chondrocyte toxicity

et al. 2022

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BackgroundT-2 toxin is recognized as one of the high-risk environmental factors for etiology and pathogenesis of Kashin-Beck disease (KBD). Previous evidence indicates decreased serum fluorine level in KBD patients. However, whether fluoride could regulate carboxylesterase 1 (CES1)-mediated T-2 toxin hydrolysis and alter its chondrocyte toxicity remains largely unknown.MethodsIn this study, in vitro hydrolytic kinetics were explored using recombinant human CES1. HPLC-MS/MS was used to quantitative determination of hydrolytic metabolites of T-2 toxin. HepG2 cells were treated with different concentration of sodium fluoride (NaF). qRT-PCR and western blot analysis were used to compare the mRNA and protein expression levels of CES1. C28/I2 cells were treated with T-2 toxin, HT-2 toxin, and neosolaniol (NEO), and then cell viability was determined by MTT assay, cell apoptosis was determined by Annexin V-FITC/PI, Hoechst 33258 staining, and cleaved caspase-3, and cell cycle was monitored by flow cytometry assay, CKD4 and CDK6.ResultsWe identified that recombinant human CES1 was involved in T-2 toxin hydrolysis to generate HT-2 toxin, but not NEO, and NaF repressed the formation of HT-2 toxin. Both mRNA and protein expression of CES1 were significantly down-regulated in a dose-dependent manner after NaF treatment in HepG2 cells. Moreover, we evaluated the chondrocyte toxicity of T-2 toxin and its hydrolytic metabolites. Results showed that T-2 toxin induced strongest cell apoptosis, followed by HT-2 toxin and NEO. The decreased the proportion of cells in G0/G1 phase was observed with the descending order of T-2 toxin, HT-2 toxin, and NEO.ConclusionsThis study reveals that CES1 is responsible for the hydrolysis of T-2 toxin, and that fluoride impairs CES1-mediated T-2 toxin detoxification to increase its chondrocyte toxicity. This study provides novel insight into understanding the relationship between fluoride and T-2 toxin in the etiology of KBD.

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Animal models of Kashin-Beck disease exposed to environmental risk factors: Methods and comparisons

Zuo

et al. 2022

Ecotoxicology and Environmental Safety

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The decreased expression of integrin αv is involved in T-2 toxin-induced extracellular matrix degradation in chondrocytes

Cited by 6 publications

References 30 publications

T-2 toxin induces articular cartilage damage by increasing the expression of MMP-13 via the TGF-β receptor pathway

T-2 toxin induces articular cartilage damage by increasing the expression of MMP-13 via the TGF-β receptor pathway

Fluorine impairs carboxylesterase 1-mediated hydrolysis of T-2 toxin and increases its chondrocyte toxicity

Animal models of Kashin-Beck disease exposed to environmental risk factors: Methods and comparisons

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