Identification of a Novel Inhibitor of the Canonical Wnt Pathway

Park, Kyoungmin; Lee, Kyungwon; Zhang, Bin; Zhou, Ti; He, Xi; Gao, Guoquan; Murray, Anne R.; Xing, Jian

doi:10.1128/mcb.01211-10

Cited by 117 publications

(135 citation statements)

References 80 publications

Supporting

Mentioning

129

Contrasting

Unclassified

Order By: Relevance

“…Although PEDF's effect on TSP-1 is one notable effect, additional mechanisms underlying PEDF's ability to maintain the integrity of the extracellular matrix remain to be investigated. A recent study 47 identified PEDF as an endogenous antagonist of LRP6, a coreceptor for the canonical Wnt-␤-catenin signaling pathway. In the liver, constitutive activation of Wnt-␤-catenin signaling yielded defective hepatocyte differentiation but fully developed bile ducts that led to remodeling of the ductal plate.…”

Section: Discussionmentioning

confidence: 99%

Pigment Epithelium-Derived Factor Regulates Early Pancreatic Fibrotic Responses and Suppresses the Profibrotic Cytokine Thrombospondin-1

Schmitz

Protiva

Gattu

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Pigment epithelium-derived factor (PEDF) is important for maintaining the normal extracellular matrix. We hypothesized that the initiation of pancreatic fibrosis is dependent on the loss of PEDF. Pancreatic PEDF expression was assessed in wild-type mice fed either a control or ethanol diet using an intragastric feeding model. Pancreatitis responses were elicited with either a single episode or a repetitive ceruleininduced (50 g/kg, 6 hourly i.p. injections) protocol in wild-type and PEDF-null mice. Quantitative realtime PCR and immunoblotting were performed to assess fibrogenic responses. In wild-type animals, PEDF expression increased with pancreatitis and was more pronounced in mice fed ethanol. Compared with wild-type mice, ␣-smooth muscle actin staining and expression levels of fibrogenic markers (eg, transforming growth factor-␤1, platelet-derived growth factor, collagen I, and thrombospondin-1) were higher in PEDF-null mice at baseline. Sirius red staining revealed more fibrosis in PEDF-null versus wildtype pancreas 1 week after pancreatitis. Differences in tissue fibrosis resolved with longer recovery periods. PEDF overexpression suppressed thrombospondin-1 levels in vitro. Ethanol feeding and experimental pancreatitis increased PEDF expression in wildtype mice. PEDF-null mice, however, demonstrated enhanced early fibrotic responses compared with wildtype mice with pancreatitis. These findings indicate that PEDF acts as a compensatory antifibrotic cytokine in

show abstract

Section: Discussionmentioning

confidence: 99%

Pigment Epithelium-Derived Factor Regulates Early Pancreatic Fibrotic Responses and Suppresses the Profibrotic Cytokine Thrombospondin-1

Schmitz

Protiva

Gattu

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…Several approaches seeking to reduce AGE interactions, either by inhibiting AGE formation, blocking AGE action, or breaking preexisting AGE cross-links, have been explored. Recently Park et al [30,79,82] have identified a novel inhibitor of the Wnt pathway that is a pigment epithelium-derived factor (PEDF), a multifunctional serine proteinase inhibitor. They have reported that overexpression of PEDF in transgenic mice as well as administration of PEDF protein attenuated Wnt signaling induced by retinal ischemia.…”

Section: Age Inhibitors and Prevention Of Retinopathymentioning

confidence: 99%

“…This drug is a potent inhibitor of AGE-mediated cross-linking and has been shown to prevent diabetic vascular complications, including diabetic retinopathy, in experimental animals [82]. Blockade of the AGE/RAGE interaction by soluble RAGE has been shown to suppress nephropathy in diabetic animals [83].…”

Section: Age Inhibitors and Prevention Of Retinopathymentioning

confidence: 99%

Molecular mechanisms of Diabetic Retinopathy, general preventive strategies and novel therapeutic targets

Safi¹,

Qvist²,

Kumar³

et al. 2013

Exp Clin Endocrinol Diabetes

View full text Add to dashboard Cite

The growing number of people with diabetes worldwide suggests that diabetic retinopathy (DR) and diabetic macular edema (DME) will continue to be sight threatening factors. The pathogenesis of diabetic retinopathy is a widespread cause of visual impairment in the world and a range of hyperglycemia-linked pathways have been implicated in the initiation and progression of this condition. Despite understanding the polyol pathway flux, activation of protein kinase C (KPC) isoforms, increased hexosamine pathway flux, and increased advanced glycation end-product (AGE) formation, pathogenic mechanisms underlying diabetes induced vision loss are not fully understood. The purpose of this paper is to review molecular mechanisms that regulate cell survival and apoptosis of retinal cells and discuss new and exciting therapeutic targets with comparison to the old and inefficient preventive strategies. This review highlights the recent advancements in understanding hyperglycemia-induced biochemical and molecular alterations, systemic metabolic factors, and aberrant activation of signaling cascades that ultimately lead to activation of a number of transcription factors causing functional and structural damage to retinal cells. It also reviews the established interventions and emerging molecular targets to avert diabetic retinopathy and its associated risk factors.

show abstract

“…We have identified the novel gene PNPLA2 in the retina that encodes a lipase-linked cell membrane protein with high affinity for PEDF and termed it PEDF-R (26). Later, other PEDF-binding proteins were reported in endothelial and tumor cells (37/67-kDa non-integrin laminin receptor (27) and cell surface F 1 F 0 -ATP synthase (28,29)) and * This work was supported, in whole or in part, by the National Institutes of on ARPE-19 cells (LRP6, a Wnt co-receptor (30)). However, it is not yet known if PEDF-R is a functional receptor for PEDF activity on the retina.…”

mentioning

confidence: 99%

Pigment Epithelium-derived Factor (PEDF) Prevents Retinal Cell Death via PEDF Receptor (PEDF-R)

Subramanian

Locatelli-Hoops

Kenealey

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: PEDF has neurotrophic activity and interacts with PEDF-R, a membrane-linked lipase. Results: A PEDF-binding region of PEDF-R is required for PEDF-R enzymatic stimulation, and peptides derived from this region block PEDF⅐PEDF-R-mediated retinal survival activities. Conclusion: A ligand binding domain is identified in PEDF-R, a critical receptor for the survival activity of PEDF. Significance: The findings provide mechanistic insight into the survival activity of PEDF.

show abstract

Identification of a Novel Inhibitor of the Canonical Wnt Pathway

Cited by 117 publications

References 80 publications

Pigment Epithelium-Derived Factor Regulates Early Pancreatic Fibrotic Responses and Suppresses the Profibrotic Cytokine Thrombospondin-1

Pigment Epithelium-Derived Factor Regulates Early Pancreatic Fibrotic Responses and Suppresses the Profibrotic Cytokine Thrombospondin-1

Molecular mechanisms of Diabetic Retinopathy, general preventive strategies and novel therapeutic targets

Pigment Epithelium-derived Factor (PEDF) Prevents Retinal Cell Death via PEDF Receptor (PEDF-R)

Contact Info

Product

Resources

About