Glyoxalase I drives epithelial-to-mesenchymal transition via argpyrimidine-modified Hsp70, miR-21 and SMAD signalling in human bronchial cells BEAS-2B chronically exposed to crystalline silica Min-U-Sil 5: Transformation into a neoplastic-like phenotype

Antognelli, Cinzia; Gambelunghe, Angela; Muzi, Giacomo; Talesa, Vincenzo Nicola

doi:10.1016/j.freeradbiomed.2016.01.009

Cited by 30 publications

(39 citation statements)

References 85 publications

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“…Our results concerning suppression of BIrc5 and rAB5c gene expressions in glioma cells after glutamine withdrawal completely agree with functional activity of proteins encoded by these genes as well as with biological significance of glutamine for glioma cells growth [15-17, 40-42, 45]. Furthermore, significant down-regulation of the expression level by glucose deprivation was shown for GLO1 gene, which has strong relation to the control of tumor growth [31][32][33][34]. Our results agree with data Hutschenreuther et al [33] that glutamine withdrawal decreases GLO1.…”

Section: Fig 3 Effect Of Glutamine Deprivation On the Expression Lesupporting

confidence: 84%

“…Furthermore, knockdown of GLO1 in the cancer cells significantly reduced tumor-associated properties such as migration and proliferation, whereas hypoxia caused inhibition of cell growth of all cells except of those over-expressing GLO1 [33]. There is data that this enzyme drives epithelial-tomesenchymal transition and is responsible for cell transformation into a neoplastic-like phenotype [34]. The heat shock protein family A (Hsp70) member 5 (HSPA5), also known as 78 kDa glucose regulated protein (GRP78) and immunoglobulin heavy chain-binding protein (BiP) protein as well as the heat shock 22 kDa protein 8 (HSPB8), also known as protein kinase H11 (H11) and small stress proteinlike protein HSP22, plays an important role in tumorigenesis [35][36][37][38][39].…”

Section: The Expression Of a Subset Of Genes Encoding Important Tumormentioning

confidence: 99%

“…Our results agree with data Hutschenreuther et al [33] that glutamine withdrawal decreases GLO1. Recently was shown that the expression of GLO1 is increased in some cancers and plays a pro-tumor role, participates in epithelial-to-mesenchymal transition, transformation into a neoplastic-like phenotype [25,34]. This enzyme metabolizes methylglyoxal, a cytotoxic metabolite, which induces the formation of advanced glycation of end-products and is increased in cancer [26].…”

Section: Fig 3 Effect Of Glutamine Deprivation On the Expression Lementioning

confidence: 99%

See 2 more Smart Citations

ERN1 modifies the effect of glutamine deprivation on tumor growth related factors expression in U87 glioma cells

Minchenko¹,

Kharkova²,

Hnatiuk³

2018

Ukr.Biochem.J

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Section: Fig 3 Effect Of Glutamine Deprivation On the Expression Lesupporting

confidence: 84%

Section: The Expression Of a Subset Of Genes Encoding Important Tumormentioning

confidence: 99%

Section: Fig 3 Effect Of Glutamine Deprivation On the Expression Lementioning

confidence: 99%

See 1 more Smart Citation

ERN1 modifies the effect of glutamine deprivation on tumor growth related factors expression in U87 glioma cells

Minchenko¹,

Kharkova²,

Hnatiuk³

2018

Ukr.Biochem.J

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“…Antognelli et al . have identified that miR-21 plays positive regulatory role in min-U-Sil 5 crystalline silica (MS5)-induced EMT in BEAS-2B cells 13 . Huleihel L et al .…”

Section: Introductionmentioning

confidence: 99%

MiR-503 modulates epithelial-mesenchymal transition in silica-induced pulmonary fibrosis by targeting PI3K p85 and is sponged by lncRNA MALAT1

Yan

Yao

et al. 2017

Sci Rep

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Silicosis is a kind of chronic, progressive and incurable lung fibrotic diseases with largely unknown and complex pathogenesis and molecular mechanisms. Mounting evidence suggests that microRNAs (miRNAs, miRs) are involved in the pathogenesis of silicosis. Our previous study based on miRNA microarray had shown that the expression levels of miR-503 were down-regulated in mouse lung tissues of silica-induced pulmonary fibrosis. Here, we validated the decreased expression of miR-503 in the fibrotic mouse lung tissues, human bronchial epithelial cells (HBE) and human lung adenocarcinoma A549 cells which were exposed to silica. In addition, overexpressed miR-503 inhibited silica-induced pulmonary fibrosis by attenuating the severity and the distribution of lesions in vivo and limiting the process of epithelial-mesenchymal transition (EMT) in vitro. Our molecular study further demonstrated that PI3K p85 is one of the target genes of miR-503 and the downstream molecules (Akt, mTOR and Snail) are tightly associated with EMT. Furthermore, the up-regulated lncRNA Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), acted as a competing endogenous RNA (ceRNA), can directly bound to miR-503, which indicated that lncRNA MALAT1 may modulate the expression of miR-503 thus triggering the activation of downstream fibrotic signaling pathways. Taken together, our data suggested that MALAT1-miR-503-PI3K/Akt/mTOR/Snail pathway plays critical roles in silica-induced pulmonary fibrosis.Silicosis, a kind of interstitial lung fibrotic disease, is incurable and irreversible, and usually caused by occupational exposure to silica dust 1, 2 . Alveolar epithelial cell injury and hyperplasia, persistent inflammation, extracellular matrix deposition and subsequent aberrant wound healing are common characteristics of silicosis 3 . In the process of pulmonary fibrosis, epithelial cells and macrophages are stimulated by the silica particles, secreting large amount of cytokines and inflammatory mediators, thus promoting epithelial cells transform to myofibroblasts through epithelial metaplasia, apoptosis, fibrocyte recruitment and EMT 4 . However, the molecular mechanisms underlying pulmonary fibrosis are still unclear.Epithelial-mesenchymal transition (EMT) means a process that polar adjacent epithelial cells transform to non-polar mesenchymal cells which lack cell-cell contacts and increase cell mobility 5 . EMT plays an important role in the development of pulmonary fibrosis and has been proved to be a valuable incident which occurs in the alveolar type II epithelial cells 6 . Myofibroblasts accumulate and secrete large amount of collagen during the formation of fibrosis, which lead to the failure of lung function. Studies have shown that pulmonary fibrosis is a process undergoing the activation of interstitial fibroblasts that convert to myofibroblasts to form the fibrotic collagen network 7 . Moreover, a population of the fibroblasts involved in the fibrotic process is thought to originate from the transition of the epithelial cel...

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“…Moreover, high glucose might also stimulate the synthesis of TGF-β through the formation of AGEs [15, 22]. AGEs are mainly formed from MGO, a byproduct of glycolysis, and are found to play an important role in EMT [23]. Studies showed that AGEs could bind to the AGE receptors on the cell membrane of rat kidney epithelial cells, and induce the expression of TGF-β which promoted EMT [24].…”

Section: Discussionmentioning

confidence: 99%

Involvement of STAT3 Signaling in High Glucose-Induced Epithelial Mesenchymal Transition in Human Peritoneal Mesothelial Cell Line HMrSV5

Zhang

Dai

Peng

2019

Kidney Blood Press Res

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Background/Aims: Peritoneal fibrosis (PF) is a common complication in patients receiving long-term peritoneal dialysis, which results in damage to peritoneal functions. Epithelial-mesenchymal transition (EMT) is a key step in the early pathogenesis of PF. Increasing evidence has shown that signal transducer and activator of transcription 3 (STAT3) signaling pathway is involved in EMT and tissue fibrosis by interacting with distinct EMT-inducing molecules, including transforming growth factor (TGF)-β and advanced glycation end products (AGEs). This study investigated the involvement of STAT3 in the PF process. Methods: We used high glucose-treated human peritoneal mesothelial cell line HMrSV5 as an in vitro model to expose the peritoneal mesothelial cells to high-glucose dialysate. Expression of EMT markers was detected by qRT-PCR. Accumulation of methylglyoxal (MGO) and AGEs in the culture supernatant were measured by enzyme-linked immunosorbent assay. Phosphorylation of STAT3 was assessed by Western blot. Results: Results showed that high glucose upregulated TGF-β, increased the productions of MGO and AGEs, and induced EMT in HMrSV5 cells. High glucose also activated the STAT3 pathway. STAT3 inhibitor reduced the high glucose-induced EMT, via reducing TGF-β expression and repressing the accumulation of MGO and AGEs. Conclusion: Our results revealed a critical role for STAT3 signaling in high glucose-induced EMT in HMrSV5 cells, and suggested that inhibition of STAT3 might be a treatment for high glucose-induced fibrogenesis in PF.

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Glyoxalase I drives epithelial-to-mesenchymal transition via argpyrimidine-modified Hsp70, miR-21 and SMAD signalling in human bronchial cells BEAS-2B chronically exposed to crystalline silica Min-U-Sil 5: Transformation into a neoplastic-like phenotype

Cited by 30 publications

References 85 publications

ERN1 modifies the effect of glutamine deprivation on tumor growth related factors expression in U87 glioma cells

ERN1 modifies the effect of glutamine deprivation on tumor growth related factors expression in U87 glioma cells

MiR-503 modulates epithelial-mesenchymal transition in silica-induced pulmonary fibrosis by targeting PI3K p85 and is sponged by lncRNA MALAT1

Involvement of STAT3 Signaling in High Glucose-Induced Epithelial Mesenchymal Transition in Human Peritoneal Mesothelial Cell Line HMrSV5

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