Interaction of Wingless Protein (Wnt), Transforming Growth Factor-β1, and Hyaluronan Production in Fetal and Postnatal Fibroblasts

Carre, Antoine L.; James, Aaron W.; Macleod, Liam C.; Kong, Wuyi; Kawai, Kenichiro; Longaker, Michael T.; Lorenz, H. Peter

doi:10.1097/prs.0b013e3181c495d1

Cited by 64 publications

(73 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, the antifibrotic TGF-β 3 with established roles in scarless healing was identified as a direct target of miR-29 (Li et al 2009), thus possibly forming complex regulatory networks between miRNAs and TGF-β signaling. Additionally, canonical Wnt and MAPK signaling pathways were recently revealed to be implicated in fetal scarless repair with uncharacterized roles (Colwell et al 2006b;Goldberg et al 2008;Carre et al 2010). These findings support the notion that sophisticated regulatory networks comprised of miRNAs and multiple signaling cascades might modulate scarless phenotypic transition and wound healing.…”

Section: Discussionsupporting

confidence: 72%

MicroRNA Profiling in Mid- and Late-Gestational Fetal Skin: Implication for Scarless Wound Healing

Cheng

Deng

et al. 2010

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 72%

MicroRNA Profiling in Mid- and Late-Gestational Fetal Skin: Implication for Scarless Wound Healing

Cheng

Deng

et al. 2010

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

“…20,29,30 Our data suggest Wnt3a induced a smooth muscle cell phenotype with increased expression of contractile proteins as well as increased expression of extracellular matrix genes. Thus, it appears Wnt3a simultaneously induced a contractile and synthetic phenotype in smooth muscle cells.…”

Section: Discussionmentioning

confidence: 82%

WNT3A induces a contractile and secretory phenotype in cultured vascular smooth muscle cells that is associated with increased gap junction communication

Carthy

Luo

McManus

2012

Laboratory Investigation

View full text Add to dashboard Cite

Evidence suggests a role for Wnt signaling in vascular wound repair and remodeling events. Despite this, very little is known about the effect of Wnt ligands on the structure and function of vascular cells. In this study, we treated vascular smooth muscle cells with 250 ng/ml of recombinant Wnt3a for 72 h and observed changes in the cell phenotype. Our data suggest Wnt3a completely alters the phenotype of vascular smooth muscle cells. The Wnt3a-treated cells appeared larger and had increased formation of stress fibers. These cells also had increased expression of the smooth muscle contractile proteins, calponin and smooth muscle a-actin, and contracted a collagen lattice faster than control cells. The Wnt3a-treated smooth muscle cells displayed increased extracellular matrix synthesis, as measured by collagen I and III mRNA expression, along with increased expression of MMP2 and MMP9, but decreased TIMP2 levels. The Wnt3a-induced change in cell phenotype was associated with increased expression of the gap junction protein connexin 43. Consistent with this, Wnt3a-treated smooth muscle cells displayed enhanced intercellular communication, as measured by the scrape-loading dye transfer technique. The canonical Wnt antagonist, dickkopf-related protein 1, completely reversed the contractile protein and connexin 43 expression seen in the Wnt3a-treated cells, suggesting these changes were dependent on canonical Wnt signaling. Collectively, this data suggest Wnt3a promotes a contractile and secretory phenotype in vascular smooth muscle cells that is associated with increased gap junction communication. Numerous studies have demonstrated that after arterial injury, vessel walls follow a response-to-injury pattern of wound healing leading to stenosis secondary to the neointimal accumulation of smooth muscle cells and extracellular matrix. 1-4 A number of soluble mediators released at the site of vascular injury act as molecular cues that guide smooth muscle cell responses during repair. 5,6 Growing evidence suggest a role for the Wnt family of secreted glycoproteins and their associated signaling pathways in regulating many of the processes involved in vascular wound repair and remodeling events. [7][8][9][10][11][12][13][14] However, the precise mechanisms and outcomes of Wnt signaling in such settings remain unclear. Moreover, the effect of specific Wnt family members on vascular cell phenotype remain undefined.The Wnt signaling pathway is best recognized for its role in the development of multi-cellular organisms, 15,16 and is critically involved in normal heart formation. 17 The Wnt family is comprised of 19 secreted glycoproteins that bind the Frizzled receptor and its co-receptor, lipoprotein receptorrelated proteins 5/6, to initiate an intracellular signaling cascade that controls the turnover of b-catenin. 18 In the absence of Wnt ligand, b-catenin is targeted for ubiquitinmediated degradation by the 26S proteasome. However, upon ligand stimulation, canonical Wnt signaling triggers a series of phosphorylation even...

show abstract

“…Moreover, an aberrant activation of this pathway has also been reported in human sclerodermic skin and in a mouse model of SSc induced by bleomycin (19). On the other hand, the Wnt family is required for conventional wound healing (39). The Wnt/b-catenin pathway is implicated in the regulation of myeloid cell motility and adhesion during wound healing (21).…”

Section: Discussionmentioning

confidence: 99%

Niclosamide Prevents Systemic Sclerosis in a Reactive Oxygen Species–Induced Mouse Model

Morin

Kavian

Nicco

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

Systemic sclerosis (SSc) is a connective tissue disorder characterized by fibrosis of the skin and inner organs, vasculopathy, and immunological abnormalities. Recent insights on the implication of STAT3, AKT, and Wnt/β-catenin in fibrosis have prompted us to investigate, in a mouse model of ROS-induced SSc, the effects of niclosamide, an antihelmintic drug that inhibits both of these signaling pathways. SSc was induced in BALB/c mice by daily s.c. injections of hypochlorous acid (HOCl). Mice were treated or not every other day, 5 d a week, for 6 wk, by niclosamide. Skin and lung fibrosis as well as immunological features were studied. Mice exposed to HOCl developed a diffuse cutaneous SSc with pulmonary fibrosis and anti-DNA topoisomerase 1 autoantibodies. STAT3, AKT, and Wnt/β-catenin pathways were hyperactivated in the skin and the lungs of diseased mice. Niclosamide reversed fibrosis of the skin and the lungs. Beneficial immunological effects were also observed because niclosamide decreased the activation of CD4+ and CD8+ T cells, autoimmune B cell activation, as well as IL-4 and IL-13 production in the skin. The improvement permitted by niclosamide in the mouse model of HOCl-induced SSc as well as the well-documented safety profile of this drug provide a rationale for the evaluation of niclosamide in the management of patients affected by this disease.

show abstract

Interaction of Wingless Protein (Wnt), Transforming Growth Factor-β1, and Hyaluronan Production in Fetal and Postnatal Fibroblasts

Abstract: Increased canonical Wnt signaling occurs during postnatal but not fetal cutaneous wound repair. Fetal and postnatal fibroblasts have a disparate response to rmWnt3a in vitro. rmWnt3a affects postnatal fibroblasts in a similar fashion to rhTGF-beta1, a known profibrotic cytokine.

Cited by 64 publications

References 38 publications

MicroRNA Profiling in Mid- and Late-Gestational Fetal Skin: Implication for Scarless Wound Healing

MicroRNA Profiling in Mid- and Late-Gestational Fetal Skin: Implication for Scarless Wound Healing

WNT3A induces a contractile and secretory phenotype in cultured vascular smooth muscle cells that is associated with increased gap junction communication

Niclosamide Prevents Systemic Sclerosis in a Reactive Oxygen Species–Induced Mouse Model

Contact Info

Product

Resources

About