Poly(ADP-ribose) polymerase-1 in high glucose-induced epithelial-mesenchymal transition during peritoneal fibrosis

Lei, Ping; Jiang, Zongpei; Zhu, Hengmei; Li, Xiaoyan; Su, Ning; Yu, Xueqing

doi:10.3892/ijmm.2011.859

Cited by 12 publications

(3 citation statements)

References 17 publications

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“…Much research showed that HG could induce epithelial-mesenchymal transition and the loss of epithelial phenotype E-cadherin was involved in the progress [19, 20]. Our results also found that HG could decrease the expression of E-cadherin compared with LG in two PC cells.…”

Section: Discussionsupporting

confidence: 74%

Indometacin Ameliorates High Glucose-Induced Proliferation and Invasion Via Modulation of E-Cadherin in Pancreatic Cancer Cells

Han

Peng

et al. 2013

CMC

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Indometacin, an inhibitor of cyclooxygenase-2 (COX-2), has been shown to exert anticancer effects in a variety of cancers. However, the effect and mechanism of indometacin on high glucose (HG)-induced proliferation and invasion of pancreatic cancer (PC) cells remain unclear. Multiple lines of evidence suggest that a large portion of pancreatic cancer (PC) patients suffer from either diabetes or HG which contributing PC progression. In this study, we report that indometacin down-regulated HG-induced proliferation and invasion via up-regulating E-cadherin but not COX-2 in PC cells. Additionally, the E-cadherin transcriptional repressors, Snail and Slug, were also involved in the process. Furthermore, the proliferation and invasion of PC cells, incubated in HG medium and treated with indometacin were significantly increased when E-cadherin was knocked down (Si-E-cad). Moreover, the protein levels of MMP-2, MMP-9, and VEGF were increased in PC cells transfected with Si-E-cad. Finally, the activation of the PI3K/AKT/GSK-3β signaling pathway was demonstrated to be involved in indometacin reversing HG-induced cell proliferation and invasion in PC cells. In conclusion, these results suggest that indometacin plays a key role in down-regulating HG-induced proliferation and invasion in PC cells. Our findings indicate that indometacin could be used as a novel therapeutic strategy to treat PC patients who simultaneously suffer from diabetes or HG.

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Section: Discussionsupporting

confidence: 74%

Indometacin Ameliorates High Glucose-Induced Proliferation and Invasion Via Modulation of E-Cadherin in Pancreatic Cancer Cells

Han

Peng

et al. 2013

CMC

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“…All doses and times of these treatments were determined in our pre-experimental results and previous study. 47 As described above, MCs were then divided into the following groups for subsequent experiments: G5, G25, G25+PJ34, G25+EX527, G25+PJ34+EX527, G25+SIRT-1 lentivirus transfected (G25+Lv-SIRT-1), G25+SIRT-1 lentivirus trans-fected+PJ34 (G25+Lv-SIRT-1+PJ34).…”

Section: Cell Culture and In Vitro Experimental Designmentioning

confidence: 99%

PARP-1 and SIRT-1 are Interacted in Diabetic Nephropathy by Activating AMPK/PGC-1α Signaling Pathway

Zhu

Fang

Chen

et al. 2021

DMSO

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Introduction: Diabetic nephropathy (DN) is a metabolic disorder characterized by the accumulation of extracellular matrix (ECM). This study aims to investigate whether exists an interplay between poly (ADP-ribose) polymerase 1 (PARP-1) and sirtuin 1 (SIRT-1) in DN via AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) signaling pathway. Methods: Eight-week-old male obese leptin-resistant (db/db) mice and nondiabetic control male C57BLKs/J (db/m) mice were used in this study. Body weight and blood glucose were evaluated after 6 h of fasting, which continues for 4 weeks. The kidney tissues were dissected for Western blot, immunofluorescence (IF) assay. Besides, PARP activity assay, MTT assay, NAD + qualification, Western blot and IF were also performed to detect the level and relation of PARP-1 and SIRT-1 in mouse mesangial cells (MCs) with or without high glucose followed by inhibiting or elevating PARP-1 and SIRT-1, respectively. Results: Western blotting shows PARP-1 and ECM marker fibronectin (FN) are upregulated while SIRT-1 is downregulated in db/db mice (p<0.05) or in mouse MCs with high glucose (p<0.05), which are significantly restored by PARP-1 inhibitor (PJ34) (p<0.05) and SIRT-1 lentiviral transfected treatment (p<0.05), or worsened by SIRT-1 inhibitor EX527 (p<0.05). PJ34 treatment (p < 0.05) or SIRT-1 overexpression (p < 0.05) could increase PGC-1α and p-AMPK levels, concomitant with down expression of FN, however, were reversed in the presence of EX527 (p<0.05). Discussion: Our results suggest an important relationship between PARP-1 and SIRT-1 through AMPK-PGC-1α pathway, indicating a potential therapeutic method for DN.

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“…There is growing evidence that ionising radiation shifts the balance between the PAI-1 vs. ID-1 (inhibitor of DNA binding-1) pathways [111] and that PARP-1 is involved in the regulation of the Smads downstream of TGF-β1 in endothelial and vascular smooth muscle cells. In animal models PARP inhibitors have been shown to alleviate fibrotic remodelling of blood arteries by inhibiting the TGF-β/Smad3 pathway [112], high glucose-induced peritoneal epithelial mesenchymal transition (EMT) and fibrosis [113], diabetic or hypertensive cardiomyopathy [114][115][116][117][118] and a variety of syndromes linked to chronic oxidative stress or exaggerated inflammation [119,120]. Taken together, these data suggest that targeting PARP-1 might be a promising therapeutic approach against vascular or pro-fibrotic diseases induced by dysregulation of the TGF-β/Smad3 pathway following irradiation.…”

Section: In Vivo Radiation Sensitivity After Parp Inhibition: Additiomentioning

confidence: 99%

Radiosensitisation by Poly(ADP-ribose) Polymerase Inhibition

Fouillade

Fouquin

Boudra

et al. 2015

Cancer Drug Discovery and Development

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Whilst the depletion of poly(ADP-ribose) polymerase (PARP) activity associated with PARP-1 and PARP-2 in cells causes radiosensitivity, its inhibition by small molecule inhibitors is showing great potential as a mechanism to potentiate the effects of radiotherapy. Indeed as over 50 % of all cancer patients will receive radiotherapy at some point in their treatment there is considerable interest in the development of radiosensitisers that can replace chemotherapeutic agents without the associated dose-limiting toxicities. Potent and specific inhibitors of PARP activity that compete with NAD + at the enzyme's activity site have been developed. Their use in preclinical in vitro and in vivo models is associated with enhanced radiosensitivity through mechanisms that not only involve the trapping of the PARP proteins at sites of strand breaks and the modulation of DNA repair in a proliferation dependent manner but also through the targeting of the endothelium and tumour vasculature and changes in tumour oxygenation and thus hypoxia-related radioresistance. However as both PARP-1 and PARP-2 are also involved in transcription regulation, chromatin modification and cellular homeostasis, the impact of PARP inhibition on these processes and long-term therapeutic responses needs to be investigated, as well as issues relating to scheduling, dose and radiation quality on the efficacy of this combined therapy.

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Poly(ADP-ribose) polymerase-1 in high glucose-induced epithelial-mesenchymal transition during peritoneal fibrosis

Cited by 12 publications

References 17 publications

Indometacin Ameliorates High Glucose-Induced Proliferation and Invasion Via Modulation of E-Cadherin in Pancreatic Cancer Cells

Indometacin Ameliorates High Glucose-Induced Proliferation and Invasion Via Modulation of E-Cadherin in Pancreatic Cancer Cells

PARP-1 and SIRT-1 are Interacted in Diabetic Nephropathy by Activating AMPK/PGC-1α Signaling Pathway

Radiosensitisation by Poly(ADP-ribose) Polymerase Inhibition

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