Nuclear factor-erythroid 2, nerve growth factor receptor, and CD34–microvessel density are differentially expressed in primary myelofibrosis, polycythemia vera, and essential thrombocythemia

Yiğit, Nuri; Covey, Shannon; Barouk-Fox, Sharon; Türker, Türker; Geyer, Julia T.; Orazi, Attilio

doi:10.1016/j.humpath.2015.05.004

Cited by 10 publications

(8 citation statements)

References 31 publications

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“…Studies have confirmed that NFE2 is an important transcriptional regulator of hemoglobin biosynthesis, normal platelet function and erythroid differentiation ( 64 , 65 ). In addition, NFE2 increases the expression levels of IL-8 to stimulate CD34 + proliferation and survival in bone marrow stromal cells, and ensure megakaryocyte proliferation and differentiation in primary myelofibrosis ( 66 ). In red blood cells (RBCs), p45NFE2 decreases ROS levels in order to protect RBCs from oxidative stress damage ( 67 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of hub genes of pneumocyte senescence induced by thoracic irradiation using weighted gene co-expression network analysis

Xing

Zhang

et al. 2015

Molecular Medicine Reports

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Irradiation commonly causes pneumocyte senescence, which may lead to severe fatal lung injury characterized by pulmonary dysfunction and respiratory failure. However, the molecular mechanism underlying the induction of pneumocyte senescence by irradiation remains to be elucidated. In the present study, weighted gene co-expression network analysis (WGCNA) was used to screen for differentially expressed genes, and to identify the hub genes and gene modules, which may be critical for senescence. A total of 2,916 differentially expressed genes were identified between the senescence and non-senescence groups following thoracic irradiation. In total, 10 gene modules associated with cell senescence were detected, and six hub genes were identified, including B-cell scaffold protein with ankyrin repeats 1, translocase of outer mitochondrial membrane 70 homolog A, actin filament-associated protein 1, Cd84, Nuf2 and nuclear factor erythroid 2. These genes were markedly associated with cell proliferation, cell division and cell cycle arrest. The results of the present study demonstrated that WGCNA of microarray data may provide further insight into the molecular mechanism underlying pneumocyte senescence.

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Section: Discussionmentioning

confidence: 99%

Identification of hub genes of pneumocyte senescence induced by thoracic irradiation using weighted gene co-expression network analysis

Xing

Zhang

et al. 2015

Molecular Medicine Reports

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“…In order to validate our hypothesis ex vivo , we selected thirteen BM trephine biopsy (BMB) from the Pathology archive of the University of Brescia. Ten normal BMB were selected from staging biopsy, negative for lymphoma; additionally, we selected three cases with diagnosis of myelofibrosis, a pathological condition known to be associated with increased expression of CD271/NGFR ( 41 ).…”

Section: Methodsmentioning

confidence: 99%

Adaptive Regulation of Osteopontin Production by Dendritic Cells Through the Bidirectional Interaction With Mesenchymal Stromal Cells

et al. 2018

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Mesenchymal stromal cells (MSCs) exert immunosuppressive effects on immune cells including dendritic cells (DCs). However, many details of the bidirectional interaction of MSCs with DCs are still unsolved and information on key molecules by which DCs can modulate MSC functions is limited. Here, we report that osteopontin (OPN), a cytokine involved in homeostatic and pathophysiologic responses, is constitutively expressed by DCs and regulated in the DC/MSC cocultures depending on the activation state of MSCs. Resting MSCs promoted OPN production, whereas the production of OPN was suppressed when MSCs were activated by proinflammatory cytokines (i.e., TNF-α, IL-6, and IL-1β). OPN induction required cell-to-cell contact, mediated at least in part, by β1 integrin (CD29). Conversely, activated MSCs inhibited the release of OPN via the production of soluble factors with a major role played by Prostaglandin E2 (PGE2). Accordingly, pretreatment with indomethacin significantly abrogated the MSC-mediated suppression of OPN while the direct addition of exogenous PGE2 inhibited OPN production by DCs. Furthermore, DC-conditioned medium promoted osteogenic differentiation of MSCs with a concomitant inhibition of adipogenesis. These effects were paralleled by the repression of the adipogenic markers PPARγ, adiponectin, and FABP4, and induction of the osteogenic markers alkaline phosphatase, RUNX2, and of the bone-anabolic chemokine CCL5. Notably, blocking OPN activity with RGD peptides or with an antibody against CD29, one of the OPN receptors, prevented the effects of DC-conditioned medium on MSC differentiation and CCL5 induction. Because MSCs have a key role in maintenance of bone marrow (BM) hematopoietic stem cell niche through reciprocal regulation with immune cells, we investigated the possible MSC/DC interaction in human BM by immunohistochemistry. Although DCs (CD1c+) are a small percentage of BM cells, we demonstrated colocalization of CD271+ MSCs with CD1c+ DCs in normal and myelodysplastic BM. OPN reactivity was observed in occasional CD1c+ cells in the proximity of CD271+ MSCs. Altogether, these results candidate OPN as a signal modulated by MSCs according to their activation status and involved in DC regulation of MSC differentiation.

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“…Three TF recognizing motifs were predicted as the binding sites for transcription factors forkhead box protein A (FOXA), specificity protein 1 (SP1), nuclear factor erythroid 2 (NFE2), respectively. NFE2 is essential for regulating erythroid and megakaryocytic maturation and differentiation 54,55 , and mutation of NFE2 was associated with polycythemia 56 . The functional convergence of NFE2 and CYP4F2 , and the observation of NFE2 binding site in the CYP4F2 promoter region implied an expressional regulation of CYP4F2 by NFE2.…”

Section: Resultsmentioning

confidence: 99%

Population Genomics Analysis Revealed Origin and High-altitude Adaptation of Tibetan Pigs

Han

Huang

et al. 2019

Sci Rep

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Tibetan pig is native to the Qinghai-Tibet Plateau and has adapted to the high-altitude environmental condition such as hypoxia. However, its origin and genetic mechanisms underlying high-altitude adaptation still remain controversial and enigmatic. Herein, we analyze 229 genomes of wild and domestic pigs from Eurasia, including 63 Tibetan pigs, and detect 49.6 million high-quality variants. Phylogenomic and structure analyses show that Tibetan pigs have a close relationship with low-land domestic pigs in China, implying a common domestication origin. Positively selected genes in Tibetan pigs involved in high-altitude physiology, such as hypoxia, cardiovascular systems, UV damage, DNA repair. Three of loci with strong signals of selection are associated with EPAS1 , CYP4F2 , and THSD7A genes, related to hypoxia and circulation. We validated four non-coding mutations nearby EPAS1 and CYP4F2 showing reduced transcriptional activity in Tibetan pigs. A high-frequency missense mutation is found in THSD7A (Lys561Arg) in Tibetan pigs. The selective sweeps in Tibetan pigs was found in association with selection against non-coding variants, indicating an important role of regulatory mutations in Tibetan pig evolution. This study is important in understanding the evolution of Tibetan pigs and advancing our knowledge on animal adaptation to high-altitude environments.

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Nuclear factor-erythroid 2, nerve growth factor receptor, and CD34–microvessel density are differentially expressed in primary myelofibrosis, polycythemia vera, and essential thrombocythemia

Cited by 10 publications

References 31 publications

Identification of hub genes of pneumocyte senescence induced by thoracic irradiation using weighted gene co-expression network analysis

Identification of hub genes of pneumocyte senescence induced by thoracic irradiation using weighted gene co-expression network analysis

Adaptive Regulation of Osteopontin Production by Dendritic Cells Through the Bidirectional Interaction With Mesenchymal Stromal Cells

Population Genomics Analysis Revealed Origin and High-altitude Adaptation of Tibetan Pigs

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