Global transcriptome study of Dip2B-deficient mouse embryonic lung fibroblast reveals its important roles in cell proliferation and development

Adlat, Salah; Sah, Rajiv Kumar; Hayel, Farooq; Yang, Chen; Bah, Fatoumata Binta; Al‐Azab, Mahmoud; Myint, May Zun Zaw; Oo, Zin Mar; Nasser, M; Zhang, Luqing; Feng, Xuechao; Zheng, Yaowu

doi:10.1016/j.csbj.2020.08.030

Cited by 10 publications

(9 citation statements)

References 43 publications

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“…A number of proteins which affect cell growth were upregulated in MSC discs. For instance Sestrin 2 (SESN2) and SH3 domain binding protein 4 (SH3BP4) are both known to negatively regulate cell proliferation through inhibition of the mammalian target of rapamycin complex 1 ( Kim et al, 2012 ; Luo et al, 2018 ), while disco-interacting protein 2 homolog B (DIP2B) may epigenetically regulate cell proliferation through DNA methylation ( Adlat et al, 2020 ). A number of upregulated proteins in MSC discs were also associated with mitochondrial protein synthesis.…”

Section: Resultsmentioning

confidence: 99%

Comparison between articular chondrocytes and mesenchymal stromal cells for the production of articular cartilage implants

Frerker

Karlsen

Stensland

et al. 2023

Front. Bioeng. Biotechnol.

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Focal lesions of articular cartilage give rise to pain and reduced joint function and may, if left untreated, lead to osteoarthritis. Implantation of in vitro generated, scaffold-free autologous cartilage discs may represent the best treatment option. Here we compare articular chondrocytes (ACs) and bone marrow-derived mesenchymal stromal cells (MSCs) for their ability to make scaffold-free cartilage discs. Articular chondrocytes produced more extracellular matrix per seeded cell than mesenchymal stromal cells. Quantitative proteomics analysis showed that articular chondrocyte discs contained more articular cartilage proteins, while mesenchymal stromal cell discs had more proteins associated with cartilage hypertrophy and bone formation. Sequencing analysis revealed more microRNAs associated with normal cartilage in articular chondrocyte discs, and large-scale target predictions, performed for the first time for in vitro chondrogenesis, suggested that differential expression of microRNAs in the two disc types were important mechanisms behind differential synthesis of proteins. We conclude that articular chondrocytes should be preferred over mesenchymal stromal cells for tissue engineering of articular cartilage.

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Section: Resultsmentioning

confidence: 99%

Comparison between articular chondrocytes and mesenchymal stromal cells for the production of articular cartilage implants

Frerker

Karlsen

Stensland

et al. 2023

Front. Bioeng. Biotechnol.

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“…Thus, observed [H 2 O 2 ] increases in previous studies may be caused by p66Shc-mediated cyt c peroxidase inhibition and O 2 - spontaneous dismutation. Ide Tx, which notably decreased myocardial [ROS], caused proteome changes consistent with caspase inhibition (Adlat et al, 2020; Cox et al, 2011; Li et al, 2002; Perez-Gomez et al ., 2020; Sugiana et al, 2008) ( Figure 4D, Table S1 ), indicating either [ROS] or p66Shc directs caspase activity in stressed environments.…”

Section: Resultsmentioning

confidence: 99%

p66Shc is an apoptotic rheostat whose targeted ROS inhibition improves MI outcomes

Haslem

Hays

Schmitz

et al. 2022

Preprint

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p66Shc is an oxidoreductase that responds to cell stress by translocating to mitochondria, where p66Shc produces pro-apoptotic reactive oxygen species (ROS). This study identifies ROS-active p66Shc as a monomer that produces superoxide anion independent of metal ions, inhibits cytochrome c peroxidase, and is regulated by environmental condition-induced structural changes. p66Shc anti-apoptotic functions, including: cytochrome c reduction, increased electron transport chain activity, and caspase cascade inhibition were also discovered. This study also demonstrates that p66Shc is a stress-dependent rheostat of apoptosis, regulated by p66Shc-mortalin complexes. These complexes decrease pro-apoptotic ROS production, without blocking p66Shc-mediated cytochrome c reduction. However, stress disrupts p66Shc-mortalin interactions, promoting apoptosis. Tipping p66Shc apoptotic balance toward anti-apoptotic functions by genetic knockdown or p66Shc-selective ROS inhibition decreased pro-apoptotic effects and improved outcomes in zebrafish myocardial infarction models, representing a potential new myocardial infarction treatment with promising results.

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“…The DIP2 family members ( DIP2A , DIP2B , and DIP2C ) are highly conserved, and DIP2B and DIP2C are both expressed in human lung and placenta (Human Protein Atlas available from http://www.proteinatlas.org ) [ 63 ]. Transcriptome profiling in lungs from Dip2a −/− versus wild-type mice revealed dysregulation of genes critical to vasculogenesis, alveologenesis, and branching morphogenesis [ 64 ], while loss of Dip2b in mice results in embryonic lethality due to abnormal lung development [ 65 , 66 ], suggesting a likely role for DIP2 members in human lung development. Further, an EWAS of lung function in a Korean COPD cohort identified one significant DMC in DIP2C (cg03559389) associated with FEV1/FVC ratio, strengthening the potential relevance of this gene in lung development and function [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of vitamin C supplementation on placental DNA methylation changes related to maternal smoking: association with gene expression and respiratory outcomes

et al. 2021

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Background Maternal smoking during pregnancy (MSDP) affects development of multiple organ systems including the placenta, lung, brain, and vasculature. In particular, children exposed to MSDP show lifelong deficits in pulmonary function and increased risk of asthma and wheeze. Our laboratory has previously shown that vitamin C supplementation during pregnancy prevents some of the adverse effects of MSDP on offspring respiratory outcomes. Epigenetic modifications, including DNA methylation (DNAm), are a likely link between in utero exposures and adverse health outcomes, and MSDP has previously been associated with DNAm changes in blood, placenta, and buccal epithelium. Analysis of placental DNAm may reveal critical targets of MSDP and vitamin C relevant to respiratory health outcomes. Results DNAm was measured in placentas obtained from 72 smokers enrolled in the VCSIP RCT: NCT03203603 (37 supplemented with vitamin C, 35 with placebo) and 24 never-smokers for reference. Methylation at one CpG, cg20790161, reached Bonferroni significance and was hypomethylated in vitamin C supplemented smokers versus placebo. Analysis of spatially related CpGs identified 93 candidate differentially methylated regions (DMRs) between treatment groups, including loci known to be associated with lung function, oxidative stress, fetal development and growth, and angiogenesis. Overlap of nominally significant differentially methylated CpGs (DMCs) in never-smokers versus placebo with nominally significant DMCs in vitamin C versus placebo identified 9059 candidate “restored CpGs” for association with placental transcript expression and respiratory outcomes. Methylation at 274 restored candidate CpG sites was associated with expression of 259 genes (FDR < 0.05). We further identified candidate CpGs associated with infant lung function (34 CpGs) and composite wheeze (1 CpG) at 12 months of age (FDR < 0.05). Increased methylation in the DIP2C, APOH/PRKCA, and additional candidate gene regions was associated with improved lung function and decreased wheeze in offspring of vitamin C-treated smokers. Conclusions Vitamin C supplementation to pregnant smokers ameliorates changes associated with maternal smoking in placental DNA methylation and gene expression in pathways potentially linked to improved placental function and offspring respiratory health. Further work is necessary to validate candidate loci and elucidate the causal pathway between placental methylation changes and outcomes of offspring exposed to MSDP. Clinical trial registration ClinicalTrials.gov, NCT01723696. Registered November 6, 2012. https://clinicaltrials.gov/ct2/show/record/NCT01723696.

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Global transcriptome study of Dip2B-deficient mouse embryonic lung fibroblast reveals its important roles in cell proliferation and development

Abstract: Graphical abstract

Cited by 10 publications

References 43 publications

Comparison between articular chondrocytes and mesenchymal stromal cells for the production of articular cartilage implants

Comparison between articular chondrocytes and mesenchymal stromal cells for the production of articular cartilage implants

p66Shc is an apoptotic rheostat whose targeted ROS inhibition improves MI outcomes

Impact of vitamin C supplementation on placental DNA methylation changes related to maternal smoking: association with gene expression and respiratory outcomes

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