Claudin-18 expression under hypoxia in neonatel lungs of brochopulmonary dysplasia model rats

Background: Bronchopulmonary dysplasia (BPD) is characterized by impaired alveolar and microvascular development. Claudin-18 is the only known lung-specific tight junction protein affecting alveolar epithelium development and transdifferentiation. Objective: To explore the changes in claudin-18 expression, alveolar epithelial cell (AEC) marker proteins, the canonical Wnt pathway, and their possible regulatory relationships in a hyperoxia-induced BPD rat model. Methods: The BPD neonatal rat model was established by exposure to hyperoxia (85%). Hematoxylin and eosin (HE) staining was used to confirm the establishment of the BPD model. The mRNA levels were assessed using quantitative real-time polymerase chain reaction, while protein expression levels were determined using western blotting, immunohistochemical staining, and immunofluorescence . Results: As confirmed by HE staining, the BPD neonatal rat model was successfully established. Compared with the air group, claudin-18 and claudin-4 expression decreased in the hyperoxia group. The expression of β-catenin of the Wnt signaling decreased, whereas that of p-GSK-3β increased. Expression of the AEC Ⅱ marker SFTPC decreased initially and then increased, whereas that of the AEC Ⅰ marker Podoplanin increased on day 14 (P < 0.05). Conclusions: Claudin-18 downregulation during hyperoxia may affect lung development and maturation, which may result in hyperoxia-induced BPD. Additionally, claudin-18 is associated with the canonical Wnt pathway and alveolar epithelial transdifferentiation.

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MicroRNA-152 modulates the canonical Wnt pathway activation by targeting DNA methyltransferase 1 in arthritic rat model

Biochimie ◽

10.1016/j.biochi.2014.08.016 ◽

2014 ◽

Vol 106 ◽

pp. 149-156 ◽

Cited By ~ 35

Author(s):

Cheng-gui Miao ◽

Ying-ying Yang ◽

Xu He ◽

Cheng Huang ◽

Yan Huang ◽

...

Keyword(s):

Rat Model ◽

Dna Methyltransferase ◽

Wnt Pathway ◽

Dna Methyltransferase 1 ◽

Canonical Wnt Pathway ◽

Pathway Activation ◽

Canonical Wnt ◽

Methyltransferase 1

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N-acetylcysteine ameliorates repetitive/stereotypic behavior due to its antioxidant properties without activation of the canonical Wnt pathway in a valproic acid-induced rat model of autism

Molecular Medicine Reports ◽

10.3892/mmr.2017.6787 ◽

2017 ◽

Vol 16 (2) ◽

pp. 2233-2240 ◽

Cited By ~ 8

Author(s):

Yinghua Zhang ◽

Weigang Cui ◽

Qianqian Zhai ◽

Tianran Zhang ◽

Xiaojun Wen

Keyword(s):

Valproic Acid ◽

Rat Model ◽

Wnt Pathway ◽

Antioxidant Properties ◽

Stereotypic Behavior ◽

Canonical Wnt Pathway ◽

Canonical Wnt

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Effects of Zidovudine Treatment on Heart mRNA Expression and Mitochondrial DNA Copy Number Associated with Alterations in Deoxynucleoside Triphosphate Composition in a Neonatal Rat Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01180-15 ◽

2015 ◽

Vol 59 (10) ◽

pp. 6328-6336 ◽

Cited By ~ 3

Author(s):

Jacob W. Snowdin ◽

Chia-Heng Hsiung ◽

Daniel G. Kesterson ◽

Vasudeva G. Kamath ◽

Edward E. McKee

Keyword(s):

Mitochondrial Dna ◽

Mrna Expression ◽

Rat Model ◽

Neonatal Rat ◽

Mrna Levels ◽

Hypertrophic Growth ◽

Hiv Therapy ◽

Mitochondrial Dna Copy Number ◽

Deoxynucleoside Triphosphate ◽

Neonatal Rat Model

ABSTRACTThe prevention of mother-to-child transmission (MTCT) of HIV is a crucial component in HIV therapy. Nucleoside reverse transcriptase inhibitors (NRTIs), primarily 3′-azido-3′-thymidine (AZT [zidovudine]), have been used to treat both mothers and neonates. While AZT is being replaced with less toxic drugs in treating mothers in MTCT prevention, it is still commonly used to treat neonates. Problems related to mitochondrial toxicity and potential mutagenesis associated with AZT treatment have been reported in treated cohorts. Yet little is known concerning the metabolism and potential toxicity of AZT on embryonic and neonatal tissues, especially considering that the enzymes of nucleoside metabolism change dramatically as many tissues convert from hyperplastic to hypertrophic growth during this period. AZT is known to inhibit thymidine phosphorylation and potentially alter deoxynucleoside triphosphate (dNTP) pools in adults. This study examines the effects of AZT on dNTP pools, mRNA expression of deoxynucleoside/deoxynucleotide metabolic enzymes, and mitochondrial DNA levels in a neonatal rat model. Results show that AZT treatment dramatically altered dNTP pools in the first 7 days of life after birth, which normalized to age-matched controls in the second and third weeks. Additionally, AZT treatment dramatically increased the mRNA levels of many enzymes involved in deoxynucleotide synthesis and mitochondrial biogenesis during the first week of life, which normalized to age-matched controls by the third week. These results were correlated with depletion of mitochondrial DNA noted in the second week. Taken together, results demonstrated that AZT treatment has a powerful effect on the deoxynucleotide synthesis pathways that may be associated with toxicity and mutagenesis.

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Activation of canonical wnt pathway promotes differentiation of mouse bone marrow-derived MSCs into type II alveolar epithelial cells, confers resistance to oxidative stress, and promotes their migration to injured lung tissue in vitro

Journal of Cellular Physiology ◽

10.1002/jcp.24282 ◽

2013 ◽

Vol 228 (6) ◽

pp. 1270-1283 ◽

Cited By ~ 42

Author(s):

Ai-ran Liu ◽

Le Liu ◽

Song Chen ◽

Yi Yang ◽

Hong-jie Zhao ◽

...

Keyword(s):

Oxidative Stress ◽

Wnt Pathway ◽

Alveolar Epithelial Cells ◽

Mouse Bone Marrow ◽

Type Ii ◽

Alveolar Epithelial ◽

Canonical Wnt Pathway ◽

Injured Lung ◽

Canonical Wnt

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Impact of the Canonical Wnt Pathway Activation on the Pathogenesis and Prognosis of Adamantinomatous Craniopharyngiomas

Hormone and Metabolic Research ◽

10.1055/a-0593-5956 ◽

2018 ◽

Vol 50 (07) ◽

pp. 575-581 ◽

Cited By ~ 4

Author(s):

Carlos Jucá ◽

Leandro Colli ◽

Clarissa Martins ◽

Marina Campanini ◽

Beatriz Paixão ◽

...

Keyword(s):

Tumor Progression ◽

Wnt Pathway ◽

Target Genes ◽

Disease Recurrence ◽

Positive Staining ◽

Mrna Levels ◽

Canonical Wnt Pathway ◽

Pathway Activation ◽

Adamantinomatous Craniopharyngioma ◽

Canonical Wnt

Abstract CTNNB1 mutations and abnormal β-catenin distribution are associated with the pathogenesis of adamantinomatous craniopharyngioma (aCP). We evaluated the expression of the canonical Wnt pathway components in aCPs and its association with CTNNB1 mutations and tumor progression. Tumor samples from 14 aCP patients and normal anterior pituitary samples from eight individuals without pituitary disease were studied. Gene expression of Wnt pathway activator (WNT4), inhibitors (SFRP1, DKK3, AXIN1, and APC), transcriptional activator (TCF7), target genes (MYC, WISP2, and, CDH1), and Wnt modulator (TP53) was evaluated by qPCR. β-Catenin, MYC, and WISP2 expression was determined by immunohistochemistry (IHC). The transcription levels of all genes studied, except APC, were higher in aCPs as compared to controls and TCF7 mRNA levels correlated with CTNNB1 mutation. CDH1 mRNA was overexpressed in tumor samples of patients with disease progression in comparison to those with stable disease. β-Catenin was positive and aberrantly distributed in 11 out of 14 tumor samples. Stronger β-catenin immunostaining associated positively with tumor progression. MYC positive staining was found in 10 out of 14 cases, whereas all aCPs were negative for WISP2. Wnt pathway genes were overexpressed in aCPs harboring CTNNB1 mutations and in patients with progressive disease. Recurrence was associated with stronger staining for β-catenin. These data suggest that Wnt pathway activation contributes to the pathogenesis and prognosis of aCPs.

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