Evidence that PI3K, Rac, Rho, and Rho kinase are involved in basic fibroblast growth factor‐stimulated fibroblast–Collagen matrix contraction

Abe, Masatoshi; Sogabe, Yoko; Syuto, Tomoko; Yokoyama, Yoko; Ishikawa, Osamu

doi:10.1002/jcb.21359

Cited by 20 publications

(21 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ERK and PI3-kinase/Akt signaling pathways are known to be involved in keratinocyte migration [21], [22]. Therefore, we next investigated the involvement of ERK and PI3-kinase/Akt signaling pathways in VPA-induced keratinocyte migration.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, these two pathways are crucial for cutaneous wound healing [6], [7]. Growth factors such as epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) accelerate keratinocyte migration and epithelialization in skin wound healing by activating the ERK and PI3-kinase/Akt signaling pathways [21], [22]. Conversely, inhibition of these signaling pathways has been shown to impair corneal wound healing [23].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Valproic Acid Induces Cutaneous Wound Healing In Vivo and Enhances Keratinocyte Motility

et al. 2012

View full text Add to dashboard Cite

BackgroundCutaneous wound healing is a complex process involving several signaling pathways such as the Wnt and extracellular signal-regulated kinase (ERK) signaling pathways. Valproic acid (VPA) is a commonly used antiepileptic drug that acts on these signaling pathways; however, the effect of VPA on cutaneous wound healing is unknown.Methods and FindingsWe created full-thickness wounds on the backs of C3H mice and then applied VPA. After 7 d, we observed marked healing and reduced wound size in VPA-treated mice. In the neo-epidermis of the wounds, β-catenin and markers for keratinocyte terminal differentiation were increased after VPA treatment. In addition, α-smooth muscle actin (α-SMA), collagen I and collagen III in the wounds were significantly increased. VPA induced proliferation and suppressed apoptosis of cells in the wounds, as determined by Ki67 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining analyses, respectively. In vitro, VPA enhanced the motility of HaCaT keratinocytes by activating Wnt/β-catenin, ERK and phosphatidylinositol 3-kinase (PI3-kinase)/Akt signaling pathways.ConclusionsVPA enhances cutaneous wound healing in a murine model and induces migration of HaCaT keratinocytes.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Valproic Acid Induces Cutaneous Wound Healing In Vivo and Enhances Keratinocyte Motility

et al. 2012

View full text Add to dashboard Cite

show abstract

“…This suggests that the reduced contractility of the Ext1 Gt/Gt fibroblasts observed in the present study may rely on a reduced signaling response to FGF2; however, this remains to be confirmed. FGF2-induced contraction of floating collagen lattices was previously shown to involve phosphatidylinositol 3-kinase, Rac, Rho, and also Rho kinase (41), implying that the intracel- lular signaling mechanisms that drive collagen gel contraction are complex and that several different signaling pathways act in parallel. HS binds to collagen I via a single binding site near the NH 2 terminus on the collagen monomer (42).…”

Section: Figure 7 Ext1mentioning

confidence: 99%

Mutation in the Heparan Sulfate Biosynthesis Enzyme EXT1 Influences Growth Factor Signaling and Fibroblast Interactions with the Extracellular Matrix

Österholm

Barczyk

Busse

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

Heparan sulfate (HS) chains bind and modulate the signaling efficiency of many ligands, including members of the fibroblast growth factor (FGF) and platelet-derived growth factor families. We previously reported the structure of HS synthesized by embryonic fibroblasts from mice with a gene trap mutation of Ext1 that encodes a glycosyltransferase involved in HS chain elongation. The gene trap mutation results in low expression of Ext1, and, as a consequence, HS chain length is substantially reduced. In the present study, Ext1 mutant and wild-type mouse embryonic fibroblasts were analyzed for the functional consequences of the Ext1 mutation for growth factor signaling and interaction with the extracellular matrix. Here, we show that the phosphorylation of ERK1/2 in response to FGF2 stimulation was markedly decreased in the Ext1 mutant fibroblasts, whereas neither PDGF-BB nor FGF10 signaling was significantly affected. Furthermore, Ext1 mutants displayed reduced ability to attach to collagen I and to contract collagen lattices, even though no differences in the expression of collagen-binding integrins were observed. Reintroduction of Ext1in the Ext1 mutant fibroblasts rescued HS chain length, FGF2 signaling, and the ability of the fibroblasts to contract collagen. These data suggest that the length of the HS chains is a critical determinant of HS-protein interactions and emphasize the essential role of EXT1 in providing specific binding sites for growth factors and extracellular matrix proteins.

show abstract

“…Lakshman et al (16) demonstrated a role for Rho kinase (ROCK) in matrix remodeling by corneal fibroblasts. Abe et al (1) showed that activation of Rho and ROCK are required for increased collagen gel contraction by dermal fibroblasts in response to basic FGF. Importantly, Shimizu et al (31) reported that Rho and its target ROCK contribute to lung fibrosis in the bleomycin mouse model and that a selective ROCK inhibitor can prevent development of fibrosis in this model.…”

Section: Discussionmentioning

confidence: 99%

Higher TRIP-1 level explains diminished collagen contraction ability of fetal versus adult fibroblasts

Navarro¹,

Rezaiekhaligh²,

Keightley³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Acute lung injury involving extremely immature lungs often heals without excessive fibrosis unlike later in gestation and in adults. Several factors may be involved, but fibroblast contraction of collagen has been linked to the level of wound fibrosis. To assess whether human lung fibroblasts of fetal versus adult origin differ in ability to contract collagen and define the molecular underpinnings, we performed three-dimensional collagen contraction assay, analyzed their differential mRNA profile, specifically for transforming growth factor-β (TGF-β) signaling pathway and extracellular matrix components, studied the cell response to TGF-β in culture, and used two-dimensional gel electrophoresis followed by mass spectrometry to identify differences in their overall proteomes. Human lung fetal fibroblasts contracted the collagen matrix less than the adults. Smooth muscle actin expression did not differ. TGF-β stimulation resulted in greater Smad3 phosphorylation in fetal compared with adults. mRNA and proteomic profiling reveal a number of TGF-β pathways, ECM components, and cytoskeletal regulatory molecules are differentially expressed between the cell types. Of note is TGF-β receptor interacting protein 1 (TRIP-1), which we show inhibits fibroblast collagen contraction and is higher in fetal than adult fibroblasts. We conclude that human lung fetal fibroblasts are less able to contract collagen than adult lung fibroblasts. The diminished ability is not due to impediment of Smad3 activation but rather, at least in part, due to their higher level of TRIP-1 expression. TRIP-1 is a novel modulator of fibroblast collagen contraction.

show abstract

Evidence that PI3K, Rac, Rho, and Rho kinase are involved in basic fibroblast growth factor‐stimulated fibroblast–Collagen matrix contraction

Cited by 20 publications

References 38 publications

Valproic Acid Induces Cutaneous Wound Healing In Vivo and Enhances Keratinocyte Motility

Valproic Acid Induces Cutaneous Wound Healing In Vivo and Enhances Keratinocyte Motility

Mutation in the Heparan Sulfate Biosynthesis Enzyme EXT1 Influences Growth Factor Signaling and Fibroblast Interactions with the Extracellular Matrix

Higher TRIP-1 level explains diminished collagen contraction ability of fetal versus adult fibroblasts

Contact Info

Product

Resources

About