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Shencun Fang, Huifang Guo, Yusi Cheng, Zewei Zhou, Wei Zhang, Bing Han, Wei Luo, Jing Wang, Weiping Xie, Jie Chao
Excessive proliferation and migration of fibroblasts contribute to pulmonary fibrosis in silicosis, and both epithelial cells and endothelial cells participate in the accumulation of fibroblasts via the epithelial-mesenchymal transition (EMT) and the endothelial-mesenchymal transition (EndMT), respectively. A mouse endothelial cell line (MML1) was exposed to silicon dioxide (SiO2 , 50 μg/cm2 ), and immunofluorescence and western blot analyses were performed to evaluate levels of specific endothelial and mesenchymal markers and to elucidate the mechanisms by which SiO2 induces the EndMT...
March 14, 2018: Cell Death & Disease
Filippo Cortesi, Gloria Delfanti, Andrea Grilli, Arianna Calcinotto, Francesca Gorini, Ferdinando Pucci, Roberta Lucianò, Matteo Grioni, Alessandra Recchia, Fabio Benigni, Alberto Briganti, Andrea Salonia, Michele De Palma, Silvio Bicciato, Claudio Doglioni, Matteo Bellone, Giulia Casorati, Paolo Dellabona
Heterotypic cellular and molecular interactions in the tumor microenvironment (TME) control cancer progression. Here, we show that CD1d-restricted invariant natural killer (iNKT) cells control prostate cancer (PCa) progression by sculpting the TME. In a mouse PCa model, iNKT cells restrained the pro-angiogenic and immunosuppressive capabilities of tumor-infiltrating immune cells by reducing pro-angiogenic TIE2+ , M2-like macrophages (TEMs), and sustaining pro-inflammatory M1-like macrophages. iNKT cells directly contacted macrophages in the PCa stroma, and iNKT cell transfer into tumor-bearing mice abated TEMs, delaying tumor progression...
March 13, 2018: Cell Reports
Dorien Reijnders, Chin-Chi Liu, Xinjing Xu, Anna Zhao, Kelsey Olson, Scott D Butler, Nataki C Douglas, Jenny L Sones
Preeclampsia (PE), a hypertensive disease of pregnancy, is a leading cause of fetal and maternal morbidity/mortality. Early angiogenic and inflammatory disturbances within the placenta are thought to underlie the development of the maternal PE syndrome and poor pregnancy outcomes. However, the exact etiology remains largely unknown. Here, we use the BPH/5 mouse model of PE to elucidate the way in which inflammation early in pregnancy contributes to abnormal expression of angiogenic factors at the maternal-fetal interface...
March 9, 2018: Physiological Genomics
Zhong Du, Hai-Long Ma, Zhi-Yuan Zhang, Jia-Wei Zheng, Yan-An Wang
A TIE2 mutation causing arginine-to-tryptophan substitution at residue 849 ( TIE2-R849W ) is commonly identified in heredofamilial venous malformation. However, there is no in vivo model to confirm the pathogenic role of TIE2-R849W . Humanized TIE2-R849W plasmid was constructed via PCR-mediated site-directed mutagenesis. After transcription and micro-injection, TIE2-R849W significantly induces multiple malformations in zebrafish: caudal vein plexus (CVP) defect, eye abnormalities, forebrain formation perturbations, and mandibular malformation...
2018: International Journal of Medical Sciences
Lulu Liu, Xiaoling Wan, Peipei Zhou, Xiaoyuan Zhou, Wei Zhang, Xinhui Hui, Xiujie Yuan, Xiaodan Ding, Ruihong Zhu, Guangxun Meng, Hui Xiao, Feng Ma, He Huang, Xianmin Song, Bin Zhou, Sidong Xiong, Yan Zhang
BACKGROUND: Adenosine triphosphate (ATP)-dependent chromatin remodeling SWI/SNF-like BAF and PBAF complexes have been implicated in the regulation of stem cell function and cancers. Several subunits of BAF or PBAF, including BRG1, BAF53a, BAF45a, BAF180, and BAF250a, are known to be involved in hematopoiesis. Baf200, a subunit of PBAF complex, plays a pivotal role in heart morphogenesis and coronary artery angiogenesis. However, little is known on the importance of Baf200 in normal and malignant hematopoiesis...
February 26, 2018: Journal of Hematology & Oncology
Philipp Kümpers, Alexander Lukasz
Pulmonary inflammation and vascular leakage are hallmarks of acute respiratory distress syndrome (ARDS), a life-threatening condition, for which there is no specific pharmacologic treatment.Recent literature suggests that leaky vessels in pulmonary infection and ARDS may be mediated through dysregulation of a non-redundant endothelial control pathway, the Tie2 receptor and its ligands, the angiopoietins.This Viewpoint summarizes results from cell-based experiments, animal models and clinical studies underlining the potential of Tie2 targeted interventions in reducing infection-mediated pulmonary hyperpermeability...
February 25, 2018: Critical Care: the Official Journal of the Critical Care Forum
Kevin Miller, Jorge A Fortun
Diabetic retinopathy and diabetic macular edema comprise a major source of visual disability throughout the developed world. The etiology and pathogenesis of macular edema is intricate and multifactorial, in which the hyperglycemic state in diabetes induces a microangiopathy. Through several inflammatory and vasogenic mediators, including vascular endothelial growth factor (VEGF) upregulation and inflammatory cytokines and chemokines, pathologic changes are induced in the vascular endothelium triggering breakdown of the blood retinal barrier, causing extravasation of fluid into the extracellular space and manifesting clinically as macular edema, resulting in visual loss...
January 2018: Asia-Pacific Journal of Ophthalmology
Rui Yan, Matijs van Meurs, Eliane R Popa, Ranran Li, Peter J Zwiers, Jan G Zijlstra, Jill Moser, Grietje Molema
Hemorrhagic shock (HS) is associated with low blood pressure due to excessive loss of circulating blood and causes both macrocirculatory and microcirculatory dysfunction. Fluid resuscitation after HS is used in the clinic to restore tissue perfusion. The persistent microcirculatory damage caused by HS and/or resuscitation can result in multiple organ damage, with the kidney being one of the involved organs. The kidney microvasculature consists of different segments that possess a remarkable heterogeneity in functional properties...
February 21, 2018: Shock
Congwen Yang, Keyi Lv, Bin Chen, Yong Yang, Xiangfa Ai, Hongfu Yu, Yihui Yang, Bin Yi, Kaizhi Lu
BACKGROUND/AIM: Increasing evidence show microRNAs (miRNAs) are associated with hepatopulmonary syndrome (HPS). The aim of this study was to investigate the role of miR-144 in the angiogenesis of HPS, as well as to identify its underlying mechanism. METHODS: The expression levels of miR-144-3p were assessed in pulmonary micro-vascular endothelial cells (PMVECs), as well as in lung tissues from rats with HPS. We predicted the potential target of miR-144-3p. Tyrosine kinase 2(Tie2) was identified as a target gene of miR144-3p, which has an essential role in the angiogenesis of lung vessel...
February 14, 2018: Experimental Cell Research
Birgitt Gutbier, Anne-Kathrin Neuhauß, Katrin Reppe, Carolin Ehrler, Ansgar Santel, Jörg Kaufmann, Markus Scholz, Norbert Weissmann, Lars Morawietz, Timothy J Mitchell, Stefano Aliberti, Stefan Hippenstiel, Norbert Suttorp, Martin Witzenrath
RATIONALE: During pneumonia, pathogen-host interaction evokes inflammation and lung barrier dysfunction. Tie2-activation by Angiopoietin-1 reduces, while Tie2-blockade by Angiopoietin-2 increases inflammation and permeability during sepsis. The role of Angiopoietin-1/-2 in pneumonia remains unidentified. OBJECTIVES: To investigate the prognostic and pathogenetic impact of Angiopoietins in regulating pulmonary vascular barrier function and inflammation in bacterial pneumonia...
February 15, 2018: American Journal of Respiratory and Critical Care Medicine
Y Li, F Zhang, W Lu, X Li
BACKGROUND: Photoreceptor cell death is a key pathology of retinal degeneration diseases. To date, the molecular mechanisms for this pathological process remain largely unclear. Junctional adhesion molecule-c (Jam-c) has been shown to play important roles in different biological events. However, its effect on retinal neuronal cells is unknown. OBJECTIVE: To determine the effect of Jam-c on adult mouse eyes, particularly, on retinal structure, vasculature and photoreceptor cells, in order to explore potential important target molecules for ocular diseases...
February 12, 2018: Current Molecular Medicine
Lynn Soong
Scrub typhus is an emerging, insect-transmitted disease caused by Orientia tsutsugamushi, a Gram- and LPS-negative bacterium that replicates freely within professional phagocytes and endothelial cells. Scrub typhus is prevalent with high mortality rates, but information regarding its molecular pathogenesis, microbial virulence determinants, and key immune responses is limited. Improved animal models have recently been developed that respectively resemble the pathological features of self-limiting or severe scrub typhus in humans...
February 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Elisabeth A Schuldt, Wolfgang Lieb, Marcus Dörr, Markus M Lerch, Henry Völzke, Matthias Nauck, Nele Friedrich
BACKGROUND: The Angiopoietin/Tie (Tyrosine kinase with Ig and EGF homology domains) signaling axis has crucial influences on angiogenesis and the vasculature's reorganization. Moreover, angiopoietin-2 (Ang2) is discussed as a biomarker for diseases' severity and development. Previous studies reported increased Ang2 levels in patients with inflammatory diseases and associations of Ang2 with inflammation markers in relatively small samples. We aimed to assess the relation of Ang2 and Tie2 with inflammation markers in the general population...
February 7, 2018: Cytokine
Stefan Liebner, Rick M Dijkhuizen, Yvonne Reiss, Karl H Plate, Dritan Agalliu, Gabriela Constantin
The adult quiescent blood-brain barrier (BBB), a structure organised by endothelial cells through interactions with pericytes, astrocytes, neurons and microglia in the neurovascular unit, is highly regulated but fragile at the same time. In the past decade, there has been considerable progress in understanding not only the molecular pathways involved in BBB development, but also BBB breakdown in neurological diseases. Specifically, the Wnt/β-catenin, retinoic acid and sonic hedgehog pathways moved into the focus of BBB research...
February 6, 2018: Acta Neuropathologica
Marianne Jäger, Astrid Hubert, Rajinikanth Gogiraju, Magdalena L Bochenek, Thomas Münzel, Katrin Schäfer
AIMS: Protein tyrosine phosphatase-1B (PTP1B) is a negative regulator of receptor tyrosine kinase signaling. In this study, we determined the importance of PTP1B expressed in endothelial cells for the vascular response to arterial injury in obesity. RESULTS: Morphometric analysis of vascular lesions generated by 10% ferric chloride (FeCl3) revealed that tamoxifen-inducible endothelial PTP1B deletion (Tie2.ERT2-Cre × PTP1Bfl/fl; End.PTP1B knockout, KO) significantly increased neointima formation, and reduced numbers of (endothelial lectin-positive) luminal cells in End...
February 1, 2018: Antioxidants & Redox Signaling
Ke Ye, Jindong Li, Xinying Li, Shi Chang, Zhejia Zhang
The angiopoietin 1 (Ang1)/angiopoietin receptor (Tie2) signaling pathway may have a notable role in the pathogenesis of inflammatory diseases. The abnormal expression of angiopoietin 1 and Tie2 has also been reported in various malignant tumors, including papillary thyroid carcinoma (PTC). However, the role and mechanism of the Ang1/Tie2 pathway in the progression of PTC remains unclear. Therefore, the aims of the present study were to clarify this. Significantly high expression levels of Ang1 and Tie2 were observed in PTC tissues and cell lines...
January 2018: Oncology Letters
Grace Mahlbacher, Louis T Curtis, John Lowengrub, Hermann B Frieboes
BACKGROUND: Immuno-oncotherapy has emerged as a promising means to target cancer. In particular, therapeutic manipulation of tumor-associated macrophages holds promise due to their various and sometimes opposing roles in tumor progression. It is established that M1-type macrophages suppress tumor progression while M2-types support it. Recently, Tie2-expressing macrophages (TEM) have been identified as a distinct sub-population influencing tumor angiogenesis and vascular remodeling as well as monocyte differentiation...
January 30, 2018: Journal for Immunotherapy of Cancer
Sarah J Higgins, Karen De Ceunynck, John Kellum, Xiuying Chen, Xuesong Gu, Sharjeel A Chaudhry, Sol Schulman, Towia A Libermann, Shulin Lu, Nathan I Shapiro, David C Christiani, Robert Flaumenhaft, Samir M Parikh
Disordered coagulation contributes to death in sepsis and lacks effective treatments. Existing markers of disseminated intravascular coagulation (DIC) reflect its sequelae rather than its causes, delaying diagnosis and treatment. Here we show that disruption of the endothelial Tie2 axis is a sentinel event in septic DIC. Proteomics in septic DIC patients revealed a network involving inflammation and coagulation with the Tie2 antagonist, Angiopoietin-2 (Angpt-2), occupying a central node. Angpt-2 was strongly associated with traditional DIC markers including platelet counts, yet more accurately predicted mortality in two large independent cohorts (combined N = 1077)...
January 23, 2018: Journal of Clinical Investigation
Tomokazu Souma, Benjamin R Thomson, Stefan Heinen, Isabel Anna Carota, Shinji Yamaguchi, Tuncer Onay, Pan Liu, Asish K Ghosh, Chengjin Li, Vera Eremina, Young-Kwon Hong, Aris N Economides, Dietmar Vestweber, Kevin G Peters, Jing Jin, Susan E Quaggin
The angiopoietin (ANGPT)-TIE2/TEK signaling pathway is essential for blood and lymphatic vascular homeostasis. ANGPT1 is a potent TIE2 activator, whereas ANGPT2 functions as a context-dependent agonist/antagonist. In disease, ANGPT2-mediated inhibition of TIE2 in blood vessels is linked to vascular leak, inflammation, and metastasis. Using conditional knockout studies in mice, we show TIE2 is predominantly activated by ANGPT1 in the cardiovascular system and by ANGPT2 in the lymphatic vasculature. Mechanisms underlying opposing actions of ANGPT2 in blood vs...
January 22, 2018: Proceedings of the National Academy of Sciences of the United States of America
Christopher Daly, Xiaozhong Qian, Carla Castanaro, Elizabeth Pasnikowski, Xiabo Jiang, Benjamin R Thomson, Susan E Quaggin, Nicholas Papadopoulos, Yang Wei, John S Rudge, Gavin Thurston, George D Yancopoulos, Samuel Davis
Angiopoietin-1 (Ang1) and Angiopoietin-2 (Ang2) are ligands for Tie2, an endothelial-specific receptor tyrosine kinase that is an essential regulator of angiogenesis. Here we report the identification, via expression cloning, of thrombomodulin (TM) as another receptor for Ang1 and Ang2. Thrombomodulin is an endothelial cell surface molecule that plays an essential role as a coagulation inhibitor via its function as a cofactor in the thrombin-mediated activation of protein C, an anticoagulant protein, as well as thrombin-activatable fibrinolysis inhibitor (TAFI)...
January 11, 2018: Scientific Reports
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