Targeted inhibition of disheveled PDZ domain via NSC668036 depresses fibrotic process

Wang, Cong; Dai, Jinghong; Sun, Zhaorui; Shi, Chaowen; Cao, Honghui; Chen, Xiang; Gu, Shen; Li, Zutong; Qian, Weiping; Han, Xiaodong

doi:10.1016/j.yexcr.2014.10.023

Cited by 40 publications

(24 citation statements)

References 39 publications

(42 reference statements)

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“…Verena and colleagues found no EMT-like signature in the transcriptome array of wnt3α-stimulated ATII cells, which indicates that whereas canonical Wnt signaling alone may not drive EMT processes, other cytokines, such as TGF-β, may exert their pro-fibrotic effects via β-catenin activation (Aumiller et al, 2013). In a previous study, we demonstrated that activated Wnt/β-catenin signaling could induce the expression of its target gene MMP-7 (Wang et al, 2015), which is one of the genes most consistently elevated in fibrotic lungs. MMP-7 has been described as a pro-fibrotic metalloproteinase (Pardo et al, 2008).…”

Section: Discussionmentioning

confidence: 98%

Inhibition of Wnt/β-catenin signaling suppresses bleomycin-induced pulmonary fibrosis by attenuating the expression of TGF-β1 and FGF-2

Chen

Shi

Meng

et al. 2016

Experimental and Molecular Pathology

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Pulmonary fibrosis is a progressive lung disorder of unknown etiology, which is characterized by alterations in alveolar epithelium function, fibroblast activation, and increased extracellular matrix deposition. Recent studies have demonstrated that PF is associated with uncontrolled production of cytokines after lung injury. In the present study, we found that transforming growth factor-β1 (TGF-β1) and fibroblast growth factor 2 (FGF-2) were both upregulated in bleomycin-induced fibrotic lung tissue and primary murine alveolar epithelial Type II (ATII) cells treated with bleomycin. Furthermore, we discovered that TGF-β1 could induce the differentiation of lung resident mesenchymal stem cells (LR-MSCs) into fibroblasts, which may play an essential role in PF. LR-MSCs incubated with FGF-2 showed modest alterations in the expression of α-SMA and Vimentin. Moreover, in our study, we found that Wnt/β-catenin signaling was activated both in vitro and in vivo as a result of bleomycin treatment. Interestingly, we also found that suppression of the Wnt/β-catenin signaling could significantly attenuate bleomycin-induced PF accompanied with decreased expression of TGF-β1 and FGF-2 in vitro and in vivo. These results support that controlling the aberrant expression of TGF-β1 and FGF-2 via inhibition of Wnt/β-catenin signaling could serve as a potential therapeutic strategy for PF.

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Section: Discussionmentioning

confidence: 98%

Inhibition of Wnt/β-catenin signaling suppresses bleomycin-induced pulmonary fibrosis by attenuating the expression of TGF-β1 and FGF-2

Chen

Shi

Meng

et al. 2016

Experimental and Molecular Pathology

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“…The experiment was performed as previously described (Wang et al, 2015). Briefly, lower left lungs were cut into 5-μm paraffin sections followed by staining with hematoxylin-eosin (H&E) for structural observation, TdT-mediated dUTP nick end labeling (TUNEL) for apoptosis, and immunofluorescence for protein regulation.…”

Section: Methodsmentioning

confidence: 99%

“…The fluorescein diacetate (FDA)/propidium iodide (PI) staining was performed as previously described (Wang et al, 2015). Cells were placed on a 24-well culture plate at 1 × 10 6 cells/ml in 0.5 ml culture medium and cultured for 12 h followed by treatment with various concentrations of MC-LR as indicated for 12 h. Next, the cells were stained with 5 μg/ml PI and 4 μg/ml FDA, followed by observation under a fluorescent microscope (Nikon ECLIPSE TE2000-S, Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

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The toxic effects of microcystin-LR on mouse lungs and alveolar type II epithelial cells

Wang

Yin

et al. 2016

Toxicon

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Objectives Microcystin-leucine arginine (MC-LR) is produced by cyanobacteria and can accumulate in lungs through blood circulation. However, the effect of MC-LR on lung remains unclear. In this study, we investigated the chronic, low-dose effect of MC-LR on mouse lung tissues and the influence of MC-LR on mouse alveolar type II epithelial cells (ATII cells). Methods MC-LR was orally administered to mice at 0, 1, 10, and 40 μg/L for 6 consecutive months and mouse lungs were obtained for histopathological and immunoblot analysis. ATII cells were cultured in various concentrations of MC-LR (0, 0.5, 5, 50, 500 nmol/L) for indicated time and the cell viability and proteins change were tested. Results Our study revealed that the chronic, low-dose MC-LR exposure induced alveolar collapse and lung cell apoptosis as well as the breach of cell junction integrity. Furthermore, following treatment with MC-LR, ATII cells could uptake MC-LR, resulting in apoptosis and disruption of cell junction integrity. Conclusions These data support the toxic potential of low-dose MC-LR in rendering chronic injury to lung tissues.

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“…The adsorption column was transferred to another DEPC-treated centrifuge tube and 50 μL RNA eluent was added; the tube was centrifuged for 30 s at 12000 rpm, and the eluate, containing the RNA, was collected. After extraction of the RNA, the quality of the isolated material was checked using 1% gel electrophoresis (Wang et al, 2015) . Table 1.…”

Section: Extraction Of Total Rna From Grass Carp Tissuesmentioning

confidence: 99%

Cloning, characterization and expression analysis of coagulation factor II gene in grass carp (Ctenopharyngodon idella)

Xu¹,

Chen²,

Yao³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Here, we characterized the structure and function of the coagulation factor II (FII) gene in grass carp and determined its role in coagulation mechanisms. The FII gene EST was obtained using a constructed splenic transcriptome database; the full-length FII gene sequence was obtained by 3' and 5' RACE. The open reading frame (ORF) of FII was cloned and the full-length gene was found to be 1718 bp, with an ORF of 1572 bp; the gene contained a 25 bp 5'-untranslated region (UTR) and 108 bp 3'-UTR. The ORF encoded 524 amino acids, including 74 alkaline amino acids (arginine and lysine) and 69 acidic amino acids (aspartic acid and glutamic acid). The theoretical pI was 6.22. The calculated instability index (II) was 39.81, indicating that FII was a stable protein; the half-life period was predicted to be approximately 30 h. Amino acid sequence comparisons indicated that grass carp FII showed most similarity (71%) to FII of Takifugu rubripes, followed by Oplegnathus fasciatus (48% similarity) and Larimichthys crocea (47% similarity). A real-time reverse transcription PCR analysis showed that under normal 13765 FII gene and grass carp ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 13764-13778 (2015) circumstances, FII was most highly expressed in the liver, followed by the gill, spleen, thymus, and head-kidney (P < 0.001). After injection of the grass carp reovirus 873 (GCRV873), the pattern of FII expression was significantly altered (P < 0.001); gene expression was high after injection, suggesting a response involving the initiation of the coagulation system and defense of the body in combination with the platelet and complement system.

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Targeted inhibition of disheveled PDZ domain via NSC668036 depresses fibrotic process

Cited by 40 publications

References 39 publications

Inhibition of Wnt/β-catenin signaling suppresses bleomycin-induced pulmonary fibrosis by attenuating the expression of TGF-β1 and FGF-2

Inhibition of Wnt/β-catenin signaling suppresses bleomycin-induced pulmonary fibrosis by attenuating the expression of TGF-β1 and FGF-2

The toxic effects of microcystin-LR on mouse lungs and alveolar type II epithelial cells

Cloning, characterization and expression analysis of coagulation factor II gene in grass carp (Ctenopharyngodon idella)

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