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61.
62.
Joan Rhl Zoe E. West Maren Rudolph Andreea Zaharia Derek Van Lonkhuyzen Danica K. Hickey Annalese B. T. Semmler Rachael Z. Murray 《Traffic (Copenhagen, Denmark)》2019,20(9):661-673
Macrophage migration into injured or infected tissue is a key aspect in the pathophysiology of many diseases where inflammation is a driving factor. Membrane‐type‐1 matrix metalloproteinase (MT1‐MMP) cleaves extracellular matrix components to facilitate invasion. Here we show that, unlike the constitutive MT1‐MMP surface recycling seen in cancer cells, unactivated macrophages express low levels of MT1‐MMP. Upon lipopolysaccharide (LPS) activation, MT1‐MMP synthesis dramatically increases 10‐fold at the surface by 15 hours. MT1‐MMP is trafficked from the Golgi complex to the surface via late endosomes/lysosomes in a pathway regulated by the late endosome/lysosome R‐SNAREs VAMP7 and VAMP8. These form two separate complexes with the surface Q‐SNARE complex Stx4/SNAP23 to regulate MT1‐MMP delivery to the plasma membrane. Loss of either one of these SNAREs leads to a reduction in surface MT1‐MMP, gelatinase activity and reduced invasion. Thus, inhibiting MT1‐MMP transport through this pathway could reduce macrophage migration and the resulting inflammation. 相似文献
63.
《Structure (London, England : 1993)》2019,27(8):1308-1315.e3
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64.
成纤维细胞生长因子9(fibroblast growth factor 9, FGF9)是成纤维细胞生长因子(fibroblast growth factor,FGF)家族成员之一,属于一种自分泌或旁分泌生长因子。在脑组织中,FGF9主要表达于海马和皮质区,具有促进细胞增殖和维持细胞存活的功能。研究发现,FGF家族在抑郁症患者的多个脑区出现表达紊乱,FGF9在抑郁行为中扮演着负调控角色,但其介导抑郁行为的分子机制尚不清楚。本文综述了FGF9及其家族成员在抑郁中的作用; 围绕其受体(FGFR)信号在中枢神经系统中的功能特点,深入分析FGF9调节抑郁行为中的作用机制;结合运动抗抑郁的神经营养假说,提出经由FGFR/GSK3β/β-catenin通路的FGF信号,可能介导抑郁症的运动干预机制的假设。这些将为FGF9介导抑郁行为和运动抗抑郁的有关研究提供理论的基础和探索的思路。 相似文献
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66.
Rappolee DA 《Developmental biology》2007,304(1):1-8
Stress enzymes triggered by transient stress mediate reprioritization of developmental and homeostatic events to flexibly accomplish the next essential developmental event. This review analyzes recent studies on stress and stress enzyme function during early mammalian development and describes the diverse consequences that result from measurement, analysis of function, and management of stress and stress enzymes during development. 相似文献
67.
68.
FGF9 regulates early hypertrophic chondrocyte differentiation and skeletal vascularization in the developing stylopod 总被引:1,自引:0,他引:1
Gain-of-function mutations in fibroblast growth factor (FGF) receptors result in chondrodysplasia and craniosynostosis syndromes, highlighting the critical role for FGF signaling in skeletal development. Although the FGFRs involved in skeletal development have been well characterized, only a single FGF ligand, FGF18, has been identified that regulates skeletal development during embryogenesis. Here we identify Fgf9 as a second FGF ligand that is critical for skeletal development. We show that Fgf9 is expressed in the proximity of developing skeletal elements and that Fgf9-deficient mice exhibit rhizomelia (a disproportionate shortening of proximal skeletal elements), which is a prominent feature of patients with FGFR3-induced chondrodysplasia syndromes. Although Fgf9 is expressed in the apical ectodermal ridge in the limb bud, we demonstrate that the Fgf9-/- limb phenotype results from loss of FGF9 functions after formation of the mesenchymal condensation. In developing stylopod elements, FGF9 promotes chondrocyte hypertrophy at early stages and regulates vascularization of the growth plate and osteogenesis at later stages of skeletal development. 相似文献
69.
Expression of adiponectin in choroidal tissue and inhibition of laser induced choroidal neovascularization by adiponectin 总被引:4,自引:0,他引:4
Bora PS Kaliappan S Lyzogubov VV Tytarenko RG Thotakura S Viswanathan T Bora NS 《FEBS letters》2007,581(10):1977-1982
The aim of this study was to investigate the role of adiponectin (APN) in a mouse model of laser induced choroidal neovascularization (CNV). We have shown by immunohistochemistry that the expression of APN, adiponectin receptor 1, adiponectin receptor 2 and T cadherin gradually increased from day 1 to day 7 post-laser in laser treated mice compared to controls. Recombinant APN (rAPN) was injected intraperitoneally (i.p., 25 microg/mouse) or intravitreally (2 microg/eye) in lasered mice. Another set of lasered mice received APN peptide via i.p. (75 microg/mouse) or intravitreal (30 microg/eye) route. Control mice received a similar treatment with PBS, control protein or control peptide after laser treatment. We found that in the i.p. and intravitreal injection of rAPN resulted in 78% and 68% inhibition respectively in the size of CNV complex compared to control mice. Similar results were observed when APN peptide was injected intravitreally or i.p. Treatment with rAPN or the peptide resulted in decreased levels of vascular endothelial growth factor. Thus, APN inhibited choroidal angiogenesis and may have therapeutic implications in the treatment of wet age related macular degeneration. 相似文献
70.
Manton KJ Haupt LM Vengadasalam K Nurcombe V Cool SM 《Journal of molecular histology》2007,38(5):415-424
Summary Understanding the complex mechanisms underlying bone remodeling is crucial to the development of novel therapeutics. Glycosaminoglycans
(GAGs) localised to the extracellular matrix (ECM) of bone are thought to play a key role in mediating aspects of bone development.
The influence of isolated GAGs was studied by utilising in vitro murine calvarial monolayer and organ culture model systems.
Addition of GAG preparations extracted from the cell surface of human osteoblasts at high concentrations (5 μg/ml) resulted
in decreased proliferation of cells and decreased suture width and number of bone lining cells in calvarial sections. When
we investigated potential interactions between the growth factors fibroblast growth factor-2 (FGF2), bone morphogenic protein-2
(BMP2) and transforming growth factor-β1 (TGFβ1) and the isolated cell surface GAGs, differences between the two model systems
emerged. The cell culture system demonstrated a potentiating role for the isolated GAGs in the inhibition of FGF2 and TGFβ1
actions. In contrast, the organ culture system demonstrated an enhanced stimulation of TFGβ1 effects. These results emphasise
the role of the ECM in mediating the interactions between GAGs and growth factors during bone development and suggest the
GAG preparations contain potent inhibitory or stimulatory components able to mediate growth factor activity.
Kerry J. Manton and Larisa M. Haupt—Co-first authors. 相似文献