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Angiogenesis and Roles of Adhesion Molecules in Psoriatic Disease
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Asmita Hazra, Saptarshi Mandal
Maintaining the quiescence of the endothelium is far from a passive process. Homeostatic low-level autocrine signaling of VEGF, Ang1, Notch, and fibroblast growth factor (FGF) maintains the quiescent phalanx cell phenotype (Welti et al. 2013). Low-level baseline signaling is important, as shifting the balance of this signaling in either direction can activate the endothelial cell. For example, a higher level of Notch activation activates the Wnt pathway, which produces a proliferating stalk cell phenotype. Stable laminar perfusion through a vessel keeps endothelial cell metabolism at a low level by Krüppel-like factor (KLF) 2–mediated repression of glycolytic enzymes, such as fructose-2,6-bisphosphatase 3 (PFKFB3). The quiescence also includes inputs from homeobox transcription factors, for example, HOX D10, HOX A5, and Gax (growth arrest homeobox or mesenchyme homeobox [Meox2]), which suppress NFkB signaling that is downstream of many pro-angiogenic signals. The basement membrane around the endothelial layer, especially ECM molecule laminin α4 (but not α5), is capable of suppressing tip cell formation by inducing Notch signaling. The oxygen sensing machinery described below is part of the homeostatic mechanism that also fine-tunes the vessel shape to optimize tissue perfusion and oxygen levels.
MEOX2 serves as a novel biomarker associated with macrophage infiltration in oesophageal squamous cell carcinoma and other digestive system carcinomas
Published in Autoimmunity, 2021
Zhen Wang, Han Yang, Rusi Zhang, Bin Luo, Bingchen Xu, Zhihua Zhu, Peng Lin
Mesenchyme homeobox 2 (MEOX2) is a protein-coding gene, that is also known as GAX (growth arrest homeobox) and MOX2 [38]. The protein encoded by this gene is a homeodomain transcription factor, that has traditionally been regarded as essential for bone and muscle growth in embryos [39]. In recent years, MEOX2 has been shown to suppress cell proliferation and EMT (epithelial-to-mesenchymal transition) in cell models [40,41]. In addition, MEOX2 has also been reported to play vital roles in platinum-based drug resistance and EGFR-TKI (epidermal growth factor receptor- tyrosine kinase inhibitor)-based treatment responses in non-small cell lung cancer (NSCLC) patients, leading to poor prognoses in these patients [42]. However, the role of MEOX2 in immune infiltration of TME has never been described.
Identification of key biomolecules in rheumatoid arthritis through the reconstruction of comprehensive disease-specific biological networks
Published in Autoimmunity, 2020
Disease specific transcriptional and post-transcriptional regulatory networks are involved in a great diversity of regulatory components. The presence of the complex regulatory network reflect the complexity of pathologic mechanism. Therefore identification of disease associated putative regulatory biomolecules gives crucial information about molecular mechanism of RA. Based on our finding, RA associated several TFs and miRNAs were determined. One of TFs is NR4A1 which is vital for cell apoptosis and its expression profile was investigated in osteoarthritis. It was determined that NR4A1 expression was significantly elevated in osteoarthritis cartilage [65]. It was not found any information about the NR4A1 association of RA in the literature. The other key TF, MEOX2 expression was identified as maximal in endothelial cells but rapidly downregulated in response to proangiogenic and proinflammatory factors [52]. In a recent study, it was found that KLF4 plays a significant role in the pathogenesis of RA in vivo, by regulating apoptosis, cytokine and matrix metalloproteinases expression in fibroblast-like synoviocytes. They reported that targeting of KLF4 might be a novel strategy for RA treatment [53]. The other resultant TF is IRF1 was studied in RA very recently. As known, the major elements of synovial inflammation are cytokines and chemokines. Of these molecules, TNF activates fibroblast-like synoviocytes which take a role in the production of inflammatory molecules. In the study, it was figured out TNF regulates the expression of IRF1 in human fibroblast-like synoviocytes. It was revealed that IRF1 specifically drives the interferon signature in RA via STAT1 [54]. Interestingly, MYB is an oncogene and TF involved in cell cycle regulation are expressed at high levels in RA fibroblast-like synoviocytes [55]. Based on our finding, it is suggested that NR4A1 and MEOX2 are considered as novel transcriptional regulators in RA. As post-transcriptional regulators, it was found that miR-299-5p was associated with primary biliary cirrhosis which is specific autoimmune diseases [56]. miR‐146a is a negative regulator of immune responses and highly expressed in RA synovium and peripheral blood mononuclear cells. It was reported that miR‐146a prevents joint destruction in arthritic mice and it has potential as a novel therapeutic target for bone destruction in RA [66]. However, the association of miR-8078, miR-3659 and miR-6882-3p with the RA was not reported before. These miRNAs might be novel candidate molecular signatures for further translational medicine research of RA.