Mitomycin C induces apoptosis in human epidural scar fibroblasts after surgical decompression for spinal cord injury

Cao, Xiaojian; Ge, Yali; Sui, Tao; Ge, Dawei; Yang, Lei; Tang, Jian

doi:10.4103/1673-5374.205106

Cited by 12 publications

(4 citation statements)

References 53 publications

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“…To date, deployment of conjunctival autografts (Kwon & Kim, ), amniotic membrane (Rosen, ), radiotherapy (Schultze, Hinrichs, & Kimmig, ), and mitomycin C (MMC) (dos Santos Martins, de Azevedo Costa, Alves, Chammas, & Schor, ) have shown promising insights in the inhibition of pterygium recurrence. Among mentioned combination therapies, MMC seems by its anti‐fibroblastic feature (Sui et al, ) is effective on pterygium associated fibroblasts arose from EMT process which ultimately declines recurrence rate (Kim, Park, & Kim, ). Pterygium shares common features with cancer in its onset, recurrence, and especially, EMT transition (Chui et al, ).…”

Section: Discussion and Literature Reviewmentioning

confidence: 99%

Signaling roadmap to epithelial–mesenchymal transition in pterygium, TWIST1 centralized

Meshkani

Kooshan

Moghadam

et al. 2019

Journal Cellular Physiology

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Pterygium as a complex disease shares common features with other malignant cells in its onset recurrence and especially epithelial–mesenchymal transition (EMT) transition. Although using different approaches including conjunctival autografts, amniotic membrane, radiotherapy, mitomycin C (MMC) has shown promising insights in the inhibition of pterygium recurrence, it needs to be investigated in more details in molecular pathways to present adjuvant target therapy. In this study, we aimed to evaluate the expression of and then illustrate the role of signaling pathways on EMT in pterygium. Using real‐time polymerase chain reaction, the twist‐related protein 1 (TWIST1) expression was compared in primary pterygium and normal conjunctiva. This study assessed the mRNA expression, as well as the association between the clinicopathological indices and the gene expression level. The expression level of TWIST1 was overexpressed in 36% of our cohort ( n = 76). There was a significant positive correlation between recurrence with grade T, grade V and a significant negative correlation with growth activity. Our vast literature review on different signaling pathways in pterygium showed that EMT has centralization role in recurrence of this disease. Our data confirmed that EMT is important in the recurrence of pterygium samples and different signaling pathways end up activating the EMT markers. It is suggested to evaluate the environmental factors and their correlation with molecular markers to select favorable treatment for this kind of diseases.

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Section: Discussion and Literature Reviewmentioning

confidence: 99%

Signaling roadmap to epithelial–mesenchymal transition in pterygium, TWIST1 centralized

Meshkani

Kooshan

Moghadam

et al. 2019

Journal Cellular Physiology

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“…The concentration of MMC to induce cytotoxicity could be much lower in other organs. A number of studies using MMC in clinic showed its safety and effectiveness (Sui et al, 2017;Chen et al, 2019). However, in an animal study by Wu et al, injection of MMC at the concentrations of 0.5 mg/ml or 0.05 mg/ml was used in porcine models after endoscopic mucosectomy.…”

Section: Discussionmentioning

confidence: 99%

Mitomycin C Inhibits Esophageal Fibrosis by Regulating Cell Apoptosis and Autophagy via lncRNA-ATB and miR-200b

Zhang

Wang

et al. 2021

Front. Mol. Biosci.

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Benign esophageal strictures (BESs) frequently results from esophageal fibrosis. The transformation of fibroblasts into fibrocyte is an important cause of fibrosis. The treatment of fibrosis is challenging. Some previous studies have indicated the antifibrotic effect of mitomycin C (MMC). However, the mechanism of action of MMC and its optimal dose for treatment remains unclear. In the present study, the role of MMC in fighting fibrosis and its mechanism was investigated. Human esophageal fibroblast cells (HEFs)were treated without or with MMC, at 2, 5, 10 μg/ml, combining with mimic lncRNA-ATB, miR-200b inhibitor, rapamycin (RAPA), and 3-Methyladenine (3-MA). The cell viability, and cell apoptosis were evaluated. In addition, expression of apoptosis related proteins (caspase8 and caspase3), autophagy related proteins (LC3II and ATG5) and fibrosis related proteins (α-SMA collagen-1 and TGF-β) were also evaluated. Furthermore, autophagosome was observed by transmission electron microscope. Results showed that the expression of lncRNA-ATB was down-regulated and miR-200b was up-regulated after treated with MMC. And MMC induced cell apoptosis and inhibited cell autophagy. On the other hand, RAPA, mimic lncRNA-ATB and miR-200b inhibitor reduced fibrogenic effect of MMC on HEFs. Collectively, this study suggests that MMC inhibited esophageal fibrosis by regulating cell apoptosis and autophagy via downregulating lncRNA-ATB and upregulating miR-200b.

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“…Apoptosis is a type of programmed cell death that differs from necrosis ( 36 ). This process serves an important role in SCI, particularly during secondary injury.…”

Section: Discussionmentioning

confidence: 99%

Methotrexate remediates spinal cord injury inï¿½vivo and inï¿½vitro via suppression of endoplasmic reticulum stress-induced apoptosis

et al. 2018

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It has been suggested that endoplasmic reticulum stress (ERS) may induce apoptosis following spinal cord injury (SCI). Methotrexate (MTX) has been used as a long-term therapy regimen for rheumatoid arthritis. However, it is not clear whether MTX remediates SCI by inhibiting ERS. In the present study, to establish an in vitro ERS cell model, PC12 cells were pre-incubated with triglycerides (TG). MTT assays revealed that treatment with 1, 2.5, 5 and 10 µM TG decreased PC12 cell viability in a dose-dependent manner. Additionally, MTX treatment significantly reversed the TG-induced decrease in cell viability and increased apoptosis according to the flow cytometry assay (P<0.05). Notably, western blotting indicated that MTX significantly decreased levels of glucose-regulated protein (GRP)78, CCAAT-enhancer-binding protein homologous protein (CHOP) and caspase-12 expression (P<0.05), which were increased following treatment with TG. Furthermore, the in vivo role of MTX in a rat model of SCI was evaluated. The motor behavioral function of rats was improved following treatment with MTX according to Basso, Beattie and Bresnahan scoring (P<0.05). Terminal deoxynucleotidyl-transferase-mediated dUTP nick end staining indicated that there were no apoptotic cells present in sham rats. In the SCI model group, apoptotic cells were observed at day 7; however, the number of apoptotic cells was reduced following an additional 7 days of MTX administration. Furthermore, levels of ERS-associated proteins, including caspase-3, activating transcription factor 6, serine/threonine-protein kinase/endoribonuclease inositol-requiring enzyme 1 α, eukaryotic initiation factor 2 α and GRP78, were significantly increased following SCI; however, administration of MTX for 7 days significantly reversed this effect (P<0.05, P<0.01 and P<0.001). Therefore, MTX may improve SCI by suppressing ERS-induced apoptosis in vitro and in vivo.

show abstract

Mitomycin C induces apoptosis in human epidural scar fibroblasts after surgical decompression for spinal cord injury

Cited by 12 publications

References 53 publications

Signaling roadmap to epithelial–mesenchymal transition in pterygium, TWIST1 centralized

Signaling roadmap to epithelial–mesenchymal transition in pterygium, TWIST1 centralized

Mitomycin C Inhibits Esophageal Fibrosis by Regulating Cell Apoptosis and Autophagy via lncRNA-ATB and miR-200b

Methotrexate remediates spinal cord injury inï¿½vivo and inï¿½vitro via suppression of endoplasmic reticulum stress-induced apoptosis

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