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Mechanotransduction in Cardiovascular Development and Regeneration: A Genetic Zebrafish Model
Published in Juhyun Lee, Sharon Gerecht, Hanjoong Jo, Tzung Hsiai, Modern Mechanobiology, 2021
Rongsong Li, Kyung In Baek, Chih-Chiang Chang, Bill Zhou, Tzung Hsiai
The Notch signaling pathway involves a series of cell-fate determination and regulates the initiation of angiogenic sprouting [30, 31]. Upon ligand binding, Notch receptors undergo proteolytic cleavage to release the Notch intracellular cytoplasmic domain (NICD) under the regulation of enzymes in the disintegrin and metalloproteinases (ADAM) family. Following translocation to the nucleus, NICD forms a transcriptional activation complex consisting of recombination signal-binding protein for the immunoglobulin J region (Rbp-JK, also known as CSL, CBF1, suppressor of hairless, or Lag-1), mastermind-like (MAML), and forkhead box O subfamily 1 (FOXO1) (FKHR) protein to induce downstream Notch target genes, including hairy and enhancer of split-1 (Hest) and the gridlock [32]. Ablation of Notch1 causes developmental retardation, resulting in embryonic lethality [33]. Missense mutation in the Notch3 gene causes the development of the degenerative vascular disease known as cerebral autosomal–dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) [34]. Dysregulated Notch activity induces failure of vascular specification and results in abnormal endothelial proliferation, leading to the formation of a hyperplastic vascular network [33, 35]. Notch signaling is further implicated in stem cell differentiation and proliferation [32, 36–39].
Expression profiles of long non-coding RNA in mouse lung tissue exposed to radon
Published in Journal of Toxicology and Environmental Health, Part A, 2019
Jihua Nie, Jing Wu, Zhihai Chen, Yang Jiao, Jie Zhang, Hailin Tian, Jianxiang Li, Jian Tong
ErbB pathway plays an important role in the regulation of cellular proliferation, cell survival and differentiation. Dysregulation of this pathway is linked to various types of cancers (Brizzolara et al. 2017; Glogowska et al. 2017). Notch signaling pathway is involved in dysregulated cell growth, proliferation and carcinogenesis (Lee et al. 2016; Lobry et al. 2014). Functional analysis via bioinformatics in this study suggested that the genes involved in ErbB and Notch signaling pathways were upregulated. The results from our study revealed increased ErbB2 and k-Ras protein expression in lung tissue of mice exposed to radon compared to controls. It is of interest that Lu and Zeng (2017) also observed that enhanced k-Ras and p53 protein expressions to be associated with pancreatic adenocarcinoma. These observations suggested that the involvement of k-Ras and p53 protein elevation might be associated with radon-induced mouse pulmonary injury. In summary, radon exposure enriched several lncRNAs which were implicated in the regulation of mRNA expression of transcription factors may be involved in radon-induced lung carcinogenesis. However, further investigations are required to verify the network alterations between lncRNA and coding genes.
Agrochemical-mediated cardiotoxicity in zebrafish embryos/larvae: What we do and where we go
Published in Critical Reviews in Environmental Science and Technology, 2023
Yang Yang, Yue Tao, Zixu Li, Yunhe Cui, Jinzhu Zhang, Ying Zhang
At the cardiac developmental level, endocardium-specific expression of Notch signaling regulates cardiac morphogenesis by interacting with multiple signals from the myocardium and epicardium. Disturbances in normal Notch signaling expression induce congenital heart disease and cardiomyopathy (Guillermo et al., 2016; Niessen & Karsan, 2008). In contrast to in humans, Notch receptors and ligands are more abundant in zebrafish but the core activation mechanisms and functions of the Notch signaling pathway are highly conserved across species (Masek & Andersson, 2017). Unlike in the general signaling pathway, both the receptor and ligand of the Notch signaling pathway are membrane proteins, which function as contact points between two cells. When the Notch signaling pathway is activated, the Notch receptor is cleaved three times (1: in the cytoplasm, furin protease in the Golgi apparatus converts Notch protein single-chain precursors into heterodimers via calcium-dependent non-covalent bonding by cleaving the s1 site at the extracellular end of the Notch transmembrane region; 2: when the Notch ligand binds to the extracellular domain of a heterodimer translocated to the cell membrane, ADAM metalloproteinase releases part of the extracellular fragment by cleaving the S2 site on the receptor; 3: γ-secretase cleaves the S3 site on the remaining heterodimer adhered to the cell membrane and forms the Notch intracellular domain) and eventually releases this domain, which forms a transcriptional complex with the CSL in the nucleus, thereby activating expression of the relevant genes (Nemir & Pedrazzini, 2008) (Figure 4).
Differentially expressed long-chain noncoding RNAs in human neuroblastoma cell line (SH-SY5Y): Alzheimer’s disease cell model
Published in Journal of Toxicology and Environmental Health, Part A, 2019
Ming Zhang, Yuan-Qing Zhang, Xie-Ze Wei, Charles Lee, Dong-Sheng Huo, He Wang, Zhi-Ying Zhao
The significant pathways for predicting the target gene were identified according to the KEGG database. The significantly enriched pathways noted were as follows: 1) neuroactive ligand–receptor interaction; 2) antigen processing and presentation; 3) glycosaminoglycan degradation; and 4) Notch signaling pathway (Figure 6).