scholarly journals VEGF Is Involved in the Increase of Dermal Microvascular Permeability Induced by Tryptase

2012 ◽  
Vol 2012 ◽  
pp. 1-8
Author(s):  
Qianming Bai ◽  
Xiaobo Li ◽  
Xinhong Wang ◽  
Yali Xu ◽  
Li Wang ◽  
...  
Keyword(s):  
Mast Cell ◽  
Vascular Permeability ◽  
Serine Proteases ◽  
Biological Activities ◽  
Critical Role ◽  
Rt Pcr ◽  
Protein Levels ◽  
Permeability Enhancement ◽  
Catalytic Inhibitor

Tryptases are predominantly mast cell-specific serine proteases with pleiotropic biological activities and play a critical role in skin allergic reactions, which are manifested with rapid edema and increases of vascular permeability. The exact mechanisms of mast cell tryptase promoting vascular permeability, however, are unclear and, therefore, we investigated the effect and mechanism of tryptase or human mast cells (HMC-1) supernatant on the permeability of human dermal microvascular endothelial cells (HDMECs). Both tryptase and HMC-1 supernatant increased permeability of HDMECs significantly, which was resisted by tryptase inhibitor APC366 and partially reversed by anti-VEGF antibody and SU5614 (catalytic inhibitor of VEGFR). Furthermore, addition of tryptase to HDMECs caused a significant increase of mRNA and protein levels of VEGF and its receptors (Flt-1 and Flk-1) by Real-time RT-PCR and Western blot, respectively. These results strongly suggest an important role of VEGF on the permeability enhancement induced by tryptase, which may lead to novel means of controlling allergic reaction in skin.

scholarly journals YKL-40 Enhanced the Permeability of HDMECs with Histamine Through Activating Akt and p38 Pathways

2021 ◽  
Author(s):  
Peimei Zhou ◽  
Lixin Fu ◽  
Tao Chen ◽  
Lin Wang ◽  
Yonghong Lu ◽  
...  
Keyword(s):  
Mast Cell ◽  
Vascular Permeability ◽  
Mrna Level ◽  
Human Mast Cell ◽  
Microvascular Endothelial Cells ◽  
Rt Pcr ◽  
Permeability Changes ◽  
Mast Cell Line ◽  
Important Marker

Abstract Background, YKL-40 is currently considered as an important marker of endothelial dysfunction. Chronic spontaneous urticaria (CSU) is a common vascular skin disease. The increased vascular permeability play an important role in the occurrence and pathogenesis of CSU.Objective, the aim of this study is to explore the role of YKL-40 on the permeability of HDMECs.Methods, in this study, the mRNA level of YKL-40 in human mast cell line (HMC-1) were detected by RT-PCR. The effects of YKL-40 on vascular permeability, VE-cadherin release, VE-cadherin disruption in human dermal microvascular endothelial cells (HDMECs) were investigated by transwell, ELISA or immunofluorescence. The phosphorylation of VE-cadherin, p38 and Akt, in histamine plus YKL-40 treated HDMECs were detected by Western Blot.Results, we found that YKL-40 significantly promoted the permeability changes and leaded to the released, disruption of VE-cadherin in HDMECs induced by histamine. Furthermore, YKL-40 also enhanced the Akt and p38 pathways. Conclusion, we suggest that YKL-40 may serve as pro-permeability cytokines, and play a role in the pathogenesis of CSU. This study will help to further elucidate the pathogenesis of CSU and provide a new target for the development of anti-histamine resistance drugs for CSU.

scholarly journals Role of Cathepsin S in Periodontal Inflammation and Infection

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
S. Memmert ◽  
A. Damanaki ◽  
A. V. B. Nogueira ◽  
S. Eick ◽  
M. Nokhbehsaim ◽  
...  
Keyword(s):  
Periodontal Diseases ◽  
Interleukin 1 ◽  
Critical Role ◽  
Gingival Tissue ◽  
Cathepsin S ◽  
Protein Levels ◽  
Periodontal Inflammation

Cathepsin S is a cysteine protease and regulator of autophagy with possible involvement in periodontitis. The objective of this study was to investigate whether cathepsin S is involved in the pathogenesis of periodontal diseases. Human periodontal fibroblasts were cultured under inflammatory and infectious conditions elicited by interleukin-1β and Fusobacterium nucleatum, respectively. An array-based approach was used to analyze differential expression of autophagy-associated genes. Cathepsin S was upregulated most strongly and thus further studied in vitro at gene and protein levels. In vivo, gingival tissue biopsies from rats with ligature-induced periodontitis and from periodontitis patients were also analyzed at transcriptional and protein levels. Multiple gene expression changes due to interleukin-1β and F. nucleatum were observed in vitro. Both stimulants caused a significant cathepsin S upregulation. A significantly elevated cathepsin S expression in gingival biopsies from rats with experimental periodontitis was found in vivo, as compared to that from control. Gingival biopsies from periodontitis patients showed a significantly higher cathepsin S expression than those from healthy gingiva. Our findings provide original evidence that cathepsin S is increased in periodontal cells and tissues under inflammatory and infectious conditions, suggesting a critical role of this autophagy-associated molecule in the pathogenesis of periodontitis.

scholarly journals Reduced Expression of Glutathione S-Transferase α4 Promotes Vascular Neointimal Hyperplasia in CKD

2017 ◽  
Vol 29 (2) ◽  
pp. 505-517 ◽  
Author(s):  
Jinlong Luo ◽  
Guang Chen ◽  
Ming Liang ◽  
Aini Xie ◽  
Qingtian Li ◽  
...  
Keyword(s):  
Glutathione Transferase ◽  
Neointimal Hyperplasia ◽  
Critical Role ◽  
Mapk Signaling ◽  
Neointima Formation ◽  
Glutathione S Transferase ◽  
Protein Levels ◽  
Underlying Mechanisms ◽  
Arteries And Veins

Neointima formation is the leading cause of arteriovenous fistula (AVF) failure. We have shown that CKD accelerates this process by transforming the vascular smooth muscle cells (SMCs) lining the AVF from a contractile to the synthetic phenotype. However, the underlying mechanisms affecting this transformation are not clear. Previous studies have shown that the α-class glutathione transferase isozymes have an important role in regulating 4-hydroxynonenal (4-HNE)–mediated proliferative signaling of cells. Here, using both the loss- and gain-of-function approaches, we investigated the role of glutathione S-transferase α4 (GSTA4) in modulating cellular 4-HNE levels for the transformation and proliferation of SMCs. Compared with non-CKD controls, mice with CKD had downregulated expression of GSTA4 at the mRNA and protein levels, with concomitant increase in 4-HNE in arteries and veins. This effect was associated with upregulated phosphorylation of MAPK signaling pathway proteins in proliferating SMCs. Overexpressing GSTA4 blocked 4-HNE–induced SMC proliferation. Additionally, inhibitors of MAPK signaling inhibited the 4-HNE–induced responses. Compared with wild-type mice, mice lacking GSTA4 exhibited increased CKD-induced neointima formation in AVF. Transient expression of an activated form of GSTA4, achieved using a combined Tet-On/Cre induction system in mice, lowered levels of 4-HNE and reduced the proliferation of SMCs. Together, these results demonstrate the critical role of GSTA4 in blocking CKD-induced neointima formation and AVF failure.

Critical role of IgE-dependent mast cell activation in a murine model of allergic conjunctivitis

2009 ◽  
Vol 124 (4) ◽  
pp. 827-833.e2 ◽  
Author(s):  
Ken Fukuda ◽  
Masaharu Ohbayashi ◽  
Kei Morohoshi ◽  
Lane Zhang ◽  
Fu-Tong Liu ◽  
...  
Keyword(s):  
Mast Cell ◽  
Murine Model ◽  
Allergic Conjunctivitis ◽  
Cell Activation ◽  
Critical Role ◽  
Mast Cell Activation

The critical role of mast cell-derived hypoxia-inducible factor-1α in human and mice melanoma growth

2012 ◽  
Vol 132 (11) ◽  
pp. 2492-2501 ◽  
Author(s):  
Hyun-Ja Jeong ◽  
Hyun-A Oh ◽  
Sun-Young Nam ◽  
Na-Ra Han ◽  
Young-Sick Kim ◽  
...  
Keyword(s):  
Mast Cell ◽  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1Α ◽  
Melanoma Growth

scholarly journals Inhibition of Endoplasmic Reticulum Stress Reverses Synaptic Plasticity Deficits in Striatum of DYT1 Dystonia Mice

2021 ◽  
Author(s):  
Huaying Cai ◽  
Linhui Ni ◽  
Xingyue Hu ◽  
Xianjun Ding
Keyword(s):  
Endoplasmic Reticulum ◽  
Synaptic Plasticity ◽  
Er Stress ◽  
Critical Role ◽  
Stress Protein ◽  
Long Term Potentiation ◽  
Research Field ◽  
Protein Levels ◽  
Dyt1 Dystonia

Abstract Background & objectiveStriatal plasticity alterations caused by endoplasmic reticulum (ER) stress is supposed to be critically involved in the mechanism of DYT1 dystonia. In the current study, we expanded this research field by investigating the critical role of ER stress underlying synaptic plasticity impairment imposed by mutant heterozygous Tor1a+/- in a DYT1 dystonia mouse model.Methods & resultsLong-term depression (LTD) was failed to be induced, while long-term potentiation (LTP) was further strengthened in striatal spiny neurons (SPNs) from the Tor1a+/- DYT1 dystonia mice. Spine morphology analyses revealed a significant increase of both number of mushroom type spines and spine width in Tor1a+/- SPNs. In addition, increased AMPA receptor function and the reduction of NMDA/AMPA ratio in the postsynaptic of Tor1a+/- SPNs was observed, along with increased ER stress protein levels in Tor1a+/- striatum. Notably, ER stress inhibitors, tauroursodeoxycholic acid (TUDCA), could rescue LTD as well as AMPA currents.ConclusionThe current study illustrated the role of ER stress in mediating structural and functional plasticity alterations in Tor1a+/- SPNs. Inhibition of the ER stress by TUDCA is beneficial in reversing the deficits at the cellular and molecular levels. Remedy of dystonia associated neurological and motor functional impairment by ER stress inhibitors could be a recommendable therapeutic agent in clinical practice.

scholarly journals Critical role of protein kinase D in VEGF‐induced vascular permeability and angiogenesis

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Zheng Gen Jin ◽  
Jinjing Zhao ◽  
Meimei Yin ◽  
Il‐Sun Kwon ◽  
Michael Mastrangelo
Keyword(s):  
Protein Kinase ◽  
Vascular Permeability ◽  
Critical Role ◽  
Protein Kinase D
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