Effects of neurotrophins on human bronchial smooth muscle cell migration and matrix metalloproteinase-9 secretion

Dagnell, Charlotta; Kemi, Cecilia; Klominek, Julius; Eriksson, Per; Sköld, C. Magnus; Eklund, Anders; Grünewald, Johan; Höglund, Caroline Olgart

doi:10.1016/j.trsl.2007.05.001

Cited by 39 publications

(29 citation statements)

References 22 publications

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“…NGF has been suggested as a potential candidate for airway remodelling in asthma and also reported to induce smooth muscle cell proliferation [40,41], migration and differentiation of fibroblasts [42]. In this study, NGF also appeared to modulate collagen I and fibronectin expression, supported by the observations in vitro in AECII and in vivo in the NA model of Clara cell injury.…”

Section: Discussionsupporting

confidence: 81%

Nerve growth factor enhances Clara cell proliferation after lung injury

Sonar¹,

Schwinge²,

Kılıç³

et al. 2010

European Respiratory Journal

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The lung epithelia facilitate wound closure by secretion of various cytokines and growth factors. Nerve growth factor (NGF) has been well described in airway inflammation; however, its likely role in lung repair has not been examined thus far.To investigate the repair function of NGF, experiments were performed in vitro using cultured alveolar epithelial cells and in vivo using a naphthalene-induced model of Clara epithelial cell injury.Both in vitro and in vivo experiments revealed airway epithelial cell proliferation following injury to be dependent on NGF and the expression of its receptor, tropomyosin-receptor-kinase A. Additionally, NGF also augmented in vitro migration of alveolar type II cells. In vivo, transgenic mice over-expressing NGF in Clara cells (NGFtg) did not reveal any proliferation or alteration in Clara cell phenotype. However, following Clara cell specific injury, proliferation was increased in NGFtg and impaired upon inhibition of NGF. Furthermore, NGF also promoted the expression of collagen I and fibronectin in vitro and in vivo during repair, where significantly higher levels were measured in re-epithelialising NGFtg mice.Our study demonstrates that NGF promotes the proliferation of lung epithelium in vitro and the renewal of Clara cells following lung injury in vivo.

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Section: Discussionsupporting

confidence: 81%

Nerve growth factor enhances Clara cell proliferation after lung injury

Sonar¹,

Schwinge²,

Kılıç³

et al. 2010

European Respiratory Journal

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“…NMDA receptors are required for such activation, but the downstream steps that then lead to MMP activation remain unknown and presumably account for some delay. It is conceivable that the onset of MMP-9 proteolysis could occur sooner, because pro-MMP-9 is present within the neuropil (10,36) and could in theory be quickly activated by signaling molecules such as nitric oxide (37) or BDNF (38) that are released by LTP induction (39).…”

Section: Discussionmentioning

confidence: 99%

Extracellular proteolysis by matrix metalloproteinase-9 drives dendritic spine enlargement and long-term potentiation coordinately

Wang

Bozdagi

Nikitczuk

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

293

323

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Persistent dendritic spine enlargement is associated with stable long-term potentiation (LTP), and the latter is thought to underlie long-lasting memories. Extracellular proteolytic remodeling of the synaptic microenvironment could be important for such plasticity, but whether or how proteolytic remodeling contributes to persistent modifications in synapse structure and function is unknown. Matrix metalloproteinase-9 (MMP-9) is an extracellular protease that is activated perisynaptically after LTP induction and required for LTP maintenance. Here, by monitoring spine size and excitatory postsynaptic potentials (EPSPs) simultaneously with combined 2-photon time-lapse imaging and whole-cell recordings from hippocampal neurons, we find that MMP-9 is both necessary and sufficient to drive spine enlargement and synaptic potentiation concomitantly. Both structural and functional MMP-driven forms of plasticity are mediated through ␤1-containing integrin receptors, are associated with integrin-dependent cofilin inactivation within spines, and require actin polymerization. In contrast, postsynaptic exocytosis and protein synthesis are both required for MMP-9-induced potentiation, but not for initial MMP-9-induced spine expansion. However, spine expansion becomes unstable when postsynaptic exocytosis or protein synthesis is blocked, indicating that the 2 forms of plasticity are expressed independently but require interactions between them for persistence. When MMP activity is eliminated during theta-stimulation-induced LTP, both spine enlargement and synaptic potentiation are transient. Thus, MMP-mediated extracellular remodeling during LTP has an instructive role in establishing persistent modifications in both synapse structure and function of the kind critical for learning and memory.actin ͉ cofilin ͉ integrin ͉ synaptic plasticity ͉ protein synthesis L ong-lasting memory is based on long-term modifications of synapse structure and function. In hippocampal area CA1, naturalistic patterns of theta-stimulation readily induce long-term potentiation (LTP) of the excitatory, glutamatergic Schaffer collateral afferent inputs that target dendritic spines (1), which are small, actin-rich dendritic protrusions that harbor the majority of the excitatory synapses (2). Studies show that dendritic spines undergo significant morphological remodeling in association with long-lasting plasticity (3). Spine growth, for example, is associated with the induction of LTP and is thought to be important for supporting persistent changes in synaptic strength (4-6). However, little is known about signals that instruct and coordinate persistent modifications in synapse structure and function during LTP.Dendritic spine morphology and synaptic potentiation can both be dynamically modulated by proteins of the extracellular matrix (ECM) and the cell-surface proteins with which they interact, which has long fueled the idea that regulated ECM remodeling has an important role in synaptic plasticity (7). How precisely such remodeling could occur is not u...

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“…1). Investigation of TrkA expression on these cells showed TrkA expression in particular on pulmonary fibroblasts (Micera et al, 2001), airway smooth muscle cells (Dagnell et al, 2007;Freund-Michel et al, 2006;Freund-Michel & Frossard, 2008b), airway epithelial cells (Othumpangat et al, 2009), and pulmonary endothelial and vascular smooth muscle cells (Freund-Michel et al, 2010) (Fig. 1). …”

Section: Airway Structural Cellsmentioning

confidence: 94%