Lumican induces human corneal epithelial cell migration and integrin expression via ERK 1/2 signaling

Seomun, Young; Joo, Choun‐Ki

doi:10.1016/j.bbrc.2008.05.014

Cited by 42 publications

(39 citation statements)

References 20 publications

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“…cells, ERK1/2 was also demonstrated as the downstream signaling pathway of lumican by regulating cell migration and expression of integrin b 1. 15 The present study demonstrated that mechanical ventilation increased expression of lumican and ERK1/2. Using lumican-defi cient mice and EKR1/2 inhibitor, we observed reduced lung injury and the progression of EMT.…”

Section: Discussionsupporting

confidence: 60%

“…4 In addition to the effects of stabilizing the collagen network in connective tissue, proteoglycans also have proinfl ammatory effects, including binding to TGF-b and toll-like receptors and activation of ERK1/2. 4,15,18 Mechanical ventilation can increase production and fragmentation of proteoglycans and affect the transmission of stress among the ECM, cellular membrane, and cytoskeleton. 4,27 Previous studies hypoxemia, neutrophil infi ltration, free radicals, and MIP-2 and TGF-b 1 production.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14] A previous study has shown that lumican increased human corneal epithelial cell migration through the extracellular signal-regulated kinase (ERK) 1/2 pathway. 15 Epithelial-mesenchymal transition (EMT) is characterized by loss of epithelial markers (E-cadherin) and transition to a spindle-shaped morphology concurrent with the acquisition of mesenchymal markers ( a -smooth muscle actin [ a -SMA], S100A4). 2,5,16 In addition to their roles in corneal transparency and EMT of lens epithelial cells, 17 proteoglycans are involved in the alterations of lung mechanics after excessive mechanical ventilation; however, the mechanisms are unclear.…”

Section: Reduction Of Vili In Lumican-defi Cient Micementioning

confidence: 99%

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Lumican Regulates Ventilation-Induced Epithelial-Mesenchymal Transition Through Extracelluar Signal-Regulated Kinase Pathway

Chu

Hung

et al. 2013

Chest

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A cute lung injury (ALI) and its most severe manifestation, ARDS, are characterized by an initial inhomogeneous infl ammatory reaction or epithelial injury that is followed by fi broblast proliferation and extracellular matrix (ECM) accumulation. 1,2 Mechanical ventilation is required for life support in patients with ARDS; however, the potential for overdistension of the healthy parts of the lungs is great. Ventilatorinduced lung injury (VILI) is characterized by noncardiogenic pulmonary edema; release of infl ammatory cytokines; infl ux of neutrophils; and increased message for the ECM proteins , including proteoglycans. 3,4 High tidal volume (V t ) mechanical ventilation can lead to the production of infl ammatory cytokines, including tumor necrosis factor-a , IL-1 b , macrophage infl ammatory protein (MIP)-2, and transforming growth factor-b 1 (TGF-b 1 ). 5,6 Chemokines are expressed in both the acute infl ammatory response and the subsequent wound remodeling after lung injury. Previous studies demonstrated that MIP-2 induces neovascularization and promotes angiogenesis during VILI. 5,7 As a major profi brogenic Methods: Male C57BL/6 mice (either wild type or lumican null) aged 3 months and weighing between 25 and 30 g were exposed to low V T (6 mL/kg) or high V T (30 mL/kg) mechanical ventilation with room air for 2 to 8 h. Nonventilated mice were used as control subjects. Results: We found that high V T mechanical ventilation increased microvascular permeability, neutrophil infl ux, production of free radicals, MIP-2 and TGF-b 1 proteins, positive staining of a -smooth muscle actin and S100A4/fi broblast-specifi c protein-1, Masson trichrome staining and extracellular collagen, and activation of lumican and ERK1/2 in wild-type mice. Decreased staining of the epithelial marker E-cadherin was also observed. Mechanical stretch-augmented EMT was attenuated with lumican-defi cient mice and pharmacologic inhibition of ERK1/2 activity by PD98059. Conclusions: The data suggest that lumican promotes high V T mechanical ventilation-induced lung injury and EMT through the activation of the ERK1/2 pathway.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Reduction Of Vili In Lumican-defi Cient Micementioning

confidence: 99%

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Lumican Regulates Ventilation-Induced Epithelial-Mesenchymal Transition Through Extracelluar Signal-Regulated Kinase Pathway

Chu

Hung

et al. 2013

Chest

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“…As well as roles in stromal wound healing, KS-PGs play a role in the wound healing properties of the corneal epithelial and endothelial cell layers [140][141][142][143][144].…”

Section: Ks In Stromal Wound Healingmentioning

confidence: 99%

Structural and biochemical aspects of keratan sulphate in the cornea

Quantock

Young

Akama

2009

Cell. Mol. Life Sci.

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Keratan sulphate (KS) is the predominant glycosaminoglycan (GAG) in the cornea of the eye, where it exists in proteoglycan (PG) form. KS-PGs have long been thought to play a pivotal role in the establishment and maintenance of the array of regularly-spaced and uniformly- thin collagen fibrils which make up the corneal stroma. This characteristic arrangement of fibrils allows light to pass through the cornea. Indeed, perturbations to the synthesis of KS-PG core proteins in genetically altered mice lead to structural matrix alterations and corneal opacification. Similarly, mutations in enzymes responsible for the sulphation of KS-GAG chains are causative for the inherited human disease, macular corneal dystrophy, which is manifested clinically by progressive corneal cloudiness starting in young adulthood.

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“…5 Altered lumican expression could also contribute to changes in cell signaling, but its role appears to be cell lineage-dependent. Specifically, in epithelial and hematopoietic cells lumican promotes cell migration and wound healing, 25,34,36 but in mesenchymal and tumor cells, lumican inhibits migration, proliferation, and Fas-Fas ligand-mediated apoptosis. 6,41 This occurs in melanoma cells through interference of actin-focal adhesion interactions 6,31 via the b1 integrin.…”

Section: Discussionmentioning

confidence: 99%

Nucleus Pulposus Cell Response to Confined and Unconfined Compression Implicates Mechanoregulation by Fluid Shear Stress

2010

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Mechanical loading of the intervertebral disc (IVD) plays an important role in governing the function of nucleus pulposus (NP) cells. In situ, the loading environment of the NP is neither fully confined nor unconfined. To investigate the potential influences of these idealized loading modes, we utilized an alginate cell culture system to compare the effects of 1 h confined and unconfined compression on glycoprotein gene expression in mixed population NP cells. For dynamic compression, we applied 10 kPa peak stress using a sinusoidal waveform at 0.5 Hz. For static compression, displacements were applied at a constant rate and held at 20% strain. Aggrecan, laminin, fibronectin, glypican, biglycan, and fibromodulin were generally stimulated, and trends were similar between confined and unconfined compression. On the other hand, lumican expression was differentially regulated between confined and unconfined groups. More interestingly, trends under static loading were opposite that under dynamic loading; lumican was upregulated in static confined compression and in dynamic unconfined compression. We theorize that this pattern is indicative of regulation by fluid flow within loaded alginate disks. Calculations using the linear biphasic model suggest that spatial pressure gradients exist in static confined specimens for the majority of the loading duration. Using a parallel plate flow chamber, we report for the first time that NP cells are sensitive to fluid shear stress and confirm that lumican expression can be regulated by short durations of exposure to fluid shear.

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Lumican induces human corneal epithelial cell migration and integrin expression via ERK 1/2 signaling

Cited by 42 publications

References 20 publications

Lumican Regulates Ventilation-Induced Epithelial-Mesenchymal Transition Through Extracelluar Signal-Regulated Kinase Pathway

Lumican Regulates Ventilation-Induced Epithelial-Mesenchymal Transition Through Extracelluar Signal-Regulated Kinase Pathway

Structural and biochemical aspects of keratan sulphate in the cornea

Nucleus Pulposus Cell Response to Confined and Unconfined Compression Implicates Mechanoregulation by Fluid Shear Stress

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