Elevated expression of type VII collagen in the skin of patients with systemic sclerosis. Regulation by transforming growth factor-beta.

Rudnicka, Lidia; Varga, John; Christiano, Angela M.; Iozzo, Renato V.; Jimenez, Sergio A.; Uitto, Jouni

doi:10.1172/jci117154

Cited by 104 publications

(54 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Type VII collagen is normally expressed only at the dermal-epidermal junction and is a component of the anchoring fibrils at the base of the epidermis (27). In scleroderma, this collagen is more highly expressed at the dermalepidermal junction and its expression also extends into the dermis (28). Type III collagen has also been shown to be elevated in skin, and type III procollagen peptides are increased in serum and urine from scleroderma patients (29)(30)(31).…”

Section: Resultsmentioning

confidence: 99%

A modified model of graft‐versus‐host–induced systemic sclerosis (scleroderma) exhibits all major aspects of the human disease

Ruzek¹,

Jha²,

Ledbetter³

et al. 2004

Arthritis & Rheumatism

110

View full text Add to dashboard Cite

Objective. Diffuse systemic sclerosis (SSc; scleroderma) is a debilitating disease characterized by excessive dermal fibrosis with later progression to internal organs. In addition to the fibrotic component, major aspects of the disease include vascular or circulatory involvement and immune dysregulation evidenced by inflammatory cells in affected tissues and production of autoantibodies. Many animal models resembling this disease have been studied, including genetic models in mice and chickens, challenge with chemicals such as bleomycin or vinyl chloride to induce fibrosis, and models of graft-versus-host (GVH)-induced disease using certain strains of mice with differences in minor histocompatibility loci. The present studies were undertaken to determine if alteration of the induction of GVH-induced scleroderma could result in a model that more fully represented the human condition. Methods. Disease was induced by injection of spleen cells from B10.D2 mice into BALB/c mice deficient in mature T and B cells (recombination-activating gene 2 targeted). Dermal thickening, collagen deposition, vasoconstriction, and parameters of immunity were analyzed.Results. Similar to the human disease, this modified GVH model of SSc demonstrated evidence of dermal thickening, particularly in the extremities, progressive fibrosis of internal organs, vasoconstriction and altered expression of vascularity markers in skin and internal organs, early immune activation, inflammation in skin and internal organs, and autoantibody generation.Conclusion. This modified model of GVH-induced SSc exhibits all major components of human disease and is likely to contribute to better understanding of the disease mechanisms and, ultimately, improved treatments for patients.

show abstract

Section: Resultsmentioning

confidence: 99%

A modified model of graft‐versus‐host–induced systemic sclerosis (scleroderma) exhibits all major aspects of the human disease

Ruzek¹,

Jha²,

Ledbetter³

et al. 2004

Arthritis & Rheumatism

110

View full text Add to dashboard Cite

show abstract

“…Cells were subsequently washed with PBS and fixed on ice for 30 min in 4% paraformaldehyde at room temperature (82,83). Cells were blocked in PBS ϩ 5% bovine serum albumin, incubated with various antibodies for 1 h, washed in PBS, and incubated for 1 h with an appropriate secondary antibody.…”

Section: Methodsmentioning

confidence: 99%

Endorepellin-evoked Autophagy Contributes to Angiostasis

Goyal

Gubbiotti

Chery

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Endorepellin, the C-terminal domain of perlecan, is an angiostatic molecule that acts as a potent inducer of autophagy via its interaction with VEGFR2. In this study, we examined the effect of endorepellin on endothelial cells using atomic force microscopy. Soluble endorepellin caused morphological and biophysical changes such as an increase in cell surface roughness and cell height. Surprisingly, these changes were not accompanied by alterations in the endothelial cell elastic modulus. We discovered that endorepellin-induced autophagic flux led to co-localization of mammalian target of rapamycin with LC3-positive autophagosomes. Endorepellin functioned upstream of AMPactivated kinase ␣, as compound C, an inhibitor of AMP-activated kinase ␣, abrogated endorepellin-mediated activation and co-localization of Beclin 1 and LC3, thereby reducing autophagic progression. Functionally, we discovered that both endorepellin and Torin 1, a canonical autophagic inducer, blunted ex vivo angiogenesis. We conclude that autophagy is a novel mechanism by which endorepellin promotes angiostasis independent of nutrient deprivation.

show abstract

“…TGF-␤ increases the expression of various ECM components, such as collagen types I, III, VI, VII, and X, fibronectin, and proteoglycans. [2][3][4][5][6][7][8] It also inhibits the production of proteolytic enzymes that catalyze ECM degradation, while enhancing the expression of protease inhibitors. 9 As a result of these multifaceted effects, TGF-␤ is believed to play a critical role in a variety of biological processes, such as wound healing and tissue remodeling.…”

mentioning

confidence: 99%

Increased Expression of Integrin αvβ5 Induces the Myofibroblastic Differentiation of Dermal Fibroblasts

Asano

Ihn

Yamane

et al. 2006

The American Journal of Pathology

158

118

View full text Add to dashboard Cite

The biological effect of cytokines is mainly determined by the cytokine-receptor interaction, which is modulated by the concentration and the activity of cytokines and/or their receptors. Because ␣v-containing integrins can bind to and/or activate latent TGF-␤, these integrins have been thought to be involved in the pathogenesis of fibrotic disorders. Our recent observations that ␣v␤5 is up-regulated in scleroderma fibroblasts and that the transient overexpression of ␣v␤5 increases the human ␣2(I) collagen gene expression in normal fibroblasts suggest the involvement of ␣v␤5 in the self-activation system in scleroderma fibroblasts. In this study, we established stable transfectants with ␣v␤5 using normal dermal fibroblasts and demonstrated that such cells differentiated into myofibroblasts by the stimulation of autocrine TGF-␤. This observation is explained by 1) ␣v␤5 recruiting latent TGF-␤1 on the cell surface, 2) endogenous active TGF-␤ localizing on the cell surface, and 3) ␣v␤5 interacting with TGF-␤ receptors. Furthermore, blockade of ␣v␤5 reversed the myofibroblastic phenotype in scleroderma fibroblasts. These data identify a novel mechanism for the establishment of autocrine TGF-␤ signaling in dermal fibroblasts by the up-regulation of ␣v␤5 and suggest the possibility of regulating fibrotic disorders, especially scleroderma, by targeting this integrin.

show abstract

Elevated expression of type VII collagen in the skin of patients with systemic sclerosis. Regulation by transforming growth factor-beta.

Cited by 104 publications

References 43 publications

A modified model of graft‐versus‐host–induced systemic sclerosis (scleroderma) exhibits all major aspects of the human disease

A modified model of graft‐versus‐host–induced systemic sclerosis (scleroderma) exhibits all major aspects of the human disease

Endorepellin-evoked Autophagy Contributes to Angiostasis

Increased Expression of Integrin αvβ5 Induces the Myofibroblastic Differentiation of Dermal Fibroblasts

Contact Info

Product

Resources

About