TWEAK/Fn14 Signaling Involvement in the Pathogenesis of Cutaneous Disease in the MRL/lpr Model of Spontaneous Lupus

Doerner, Jessica; Wen, Jing; Xia, Yumin; Paz, Karin Blecher; Schairer, David; Wu, Lan; Chalmers, Samantha A.; Izmirly, Peter; Michaelson, Jennifer S.; Burkly, Linda C.; Friedman, Adam; Putterman, Chaim

doi:10.1038/jid.2015.124

Cited by 52 publications

(74 citation statements)

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“…The downstream cytokines, such as RANTES, MACP-1, IP-10, MIP-1α, ICAM-1, and VCAM-1, are produced locally, reflecting the activation of the TWEAK/Fn14 pathway [7-11, 21, 32]. These disorders not only present different characteristics of skin inflammation but also have cutaneous keratinocytes with diverse fates.…”

Section: Inflammatory Microenvironments Influence the Effect Of Tweakmentioning

confidence: 99%

“…TWEAK/Fn14 interaction induces death (apoptosis and necrosis) of keratinocytes in atopic dermatitis and cutaneous lupus erythematosus [8, 11, 31]. Atopic dermatitis is characterized by the production of T helper 1 (Th1) cytokines, including interferon-γ in lesional skin [32].…”

Section: Inflammatory Microenvironments Influence the Effect Of Tweakmentioning

confidence: 99%

“…This cytokine cascade recruits immune cells, exacerbates inflammation, induces the apoptosis of keratinocytes, and ultimately destroys skin tissues, resulting in the photo-induced lesions of cutaneous lupus erythematosus [34]. TWEAK/Fn14 activation is prominent in skin lesions of patients with lupus erythematosus and in MRL/lpr lupus-prone models [11, 31]. Fn14 deficiency in MRL/lpr mice attenuates ultraviolet B irradiation–induced skin lesions and apoptosis of cutaneous keratinocytes [11, 31].…”

Section: Inflammatory Microenvironments Influence the Effect Of Tweakmentioning

confidence: 99%

“…Both TWEAK and Fn14 are highly expressed in various cutaneous inflammatory disorders, including lupus erythematosus [11, 31], psoriasis [7], atopic dermatitis [8], skin warts [9], and bullous pemphigoid [10]. The downstream cytokines, such as RANTES, MACP-1, IP-10, MIP-1α, ICAM-1, and VCAM-1, are produced locally, reflecting the activation of the TWEAK/Fn14 pathway [7-11, 21, 32].…”

Section: Inflammatory Microenvironments Influence the Effect Of Tweakmentioning

confidence: 99%

“…Moreover, the same types of cells show diverse cell cycles under various microenvironments. Further, TWEAK/Fn14 signals are involved in cutaneous inflammation and diversely regulate the cell fates of keratinocytes [7-11]. In fact, the regulation of cell fates is central to the function of TWEAK/Fn14 signaling.…”

Section: Introductionmentioning

confidence: 99%

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Tumor Necrosis Factor Receptor Mediates Fibroblast Growth Factor-Inducible 14 Signaling

Wang¹,

Xiao²,

Xia³

2017

Cell Physiol Biochem

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Tumor necrosis factor (TNF)-related weak inducer of apoptosis (TWEAK) engages its sole receptor, fibroblast growth factor–inducible 14 (Fn14), which participates in various inflammatory and immunologic processes. TWEAK/Fn14 interaction induces different cell fates depending on the local microenvironment, which correlates with certain expression profiles of TNF receptors (TNFR). The predominant expression of TNFR1 or TNFR2 facilitates cell death or proliferation, respectively, on TWEAK/Fn14 activation. TNFR-associated factors (TRAF) interact with Fn14, cellular inhibitor of apoptosis protein (cIAP)-1, and TNFR, consequently transducing signals from TWEAK to downstream cytokines and cell cycle mediators. An Fn14-TRAF2-TNFR axis has been suggested in the function of TWEAK/Fn14 signaling, which may serve as a target in the development of novel therapeutic strategies for many diseases that have Fn14-overexpressing cells in affected tissues. The aims of this review are: 1) to present the main results on TWEAK/Fn14 regulation of cell fates, 2) to analyze the mechanism of the Fn14-TRAF2-TNFR axis, and 3) to summarize the potential strategies in the pharmacologic targeting of this axis.

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Section: Inflammatory Microenvironments Influence the Effect Of Tweakmentioning

confidence: 99%

Section: Inflammatory Microenvironments Influence the Effect Of Tweakmentioning

confidence: 99%

Section: Inflammatory Microenvironments Influence the Effect Of Tweakmentioning

confidence: 99%

Section: Inflammatory Microenvironments Influence the Effect Of Tweakmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Tumor Necrosis Factor Receptor Mediates Fibroblast Growth Factor-Inducible 14 Signaling

Wang¹,

Xiao²,

Xia³

2017

Cell Physiol Biochem

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Fn14

Martín‐Sánchez¹,

Fontecha‐Barriuso²,

Sánchez-Niño³

et al. 2016

Encyclopedia of Signaling Molecules

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FGR (Gene Name)

Berton¹,

Baruzzi²

2018

Encyclopedia of Signaling Molecules

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(Duh et al. 1994; Holthuis et al. 1994). The sequence analyses revealed that fascin proteins form a unique family of actin-bundling proteins, sharing no apparent homology with nonfascin actin-bundling proteins including alpha-actinin, villin, and fimbrin.Vertebrates have three fascin genes (fascin-1 through À3): fascin-1 shows widespread expression in a variety of tissues, whereas expression of fascin-2 is restricted to retina and hair cell stereocilia, whereas fascin-3 is restricted to testis. Fascin is absent in Dictyostelium discoideum, C. elegans, or yeasts. As expected from the actin-bundling activity, fascin is mainly localized in filopodia of mammalian cultured cells, microvilli of sea urchin eggs, and drosophila bristles. Consistent with highly motile structure of filopodia, fascin is shown to promote cell motility and metastasis of tumor cells. Intriguingly, a fascin homologue is found in microvilli and filopodia of choanoflagellates. Because this unicellular organism is considered as the last ancestor of multicellular animals, fascin1 is suggested to be an ancestral component for filopodial assembly machinery (Sebe-Pedros et al. 2013). Structure and Function of FascinX-ray structural analyses revealed that fascin has a b-trefoil structure (Sedeh et al. 2010), showing Fascin1 plays an important role in the formation of filopodia in mammalian cells. In vitro, fascin1 makes parallel actin bundles with uniform polarity, which is consistent with its localization in filopodia. Upregulation of fascin1 induces membrane protrusions and increases cell motility of epithelial cells, as well as colonic epithelial and carcinoma cells. Conversely, Fascin1 knock down has been reported to block filopodia assembly of B16F1 mouse melanoma cells, as well as colon carcinoma cells and mature antigen-presenting dendritic cells (DCs) (Ross et al. 1998).In addition to binding to actin filaments, fascin1 has been recently reported to bind directly to microtubules (Villari et al. 2015). Fascin1-microtubule binding occurred independently of fascin1-actin binding. The association was shown to increase the dynamics of focal adhesions, as well as that of microtubules, thereby controlling cell motility. This regulation of focal adhesion dynamics may be controlled via FAK because fascin1 was found to bind to FAK. Genetic AnalysesAnalyses of Drosophila singed mutations indicate that fascin1 is involved in female sterility, in addition to the gnarled bristle phenotype. In Drosophila oogenesis, each developing oocyte is surrounded by and connected to 15 nurse cells via intercellular bridges. Nurse cell cytoplasmic contents flow into the oocyte along actin filaments traversing these cytoplasmic bridges. A singed allele affects the microfilament structure required for this nurse cell cytoplasmic flow, resulting in female sterility (Cant et al. 1994). Interestingly, fascin1 is involved in prostaglandin-mediated actin remodeling (Groen et al. 2012). Prostaglandin is synthesized in Drosophila by peroxidase (Pxt), a cyclooxygenase (COX)-like...

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TWEAK/Fn14 Signaling Involvement in the Pathogenesis of Cutaneous Disease in the MRL/lpr Model of Spontaneous Lupus

Cited by 52 publications

References 53 publications

Tumor Necrosis Factor Receptor Mediates Fibroblast Growth Factor-Inducible 14 Signaling

Tumor Necrosis Factor Receptor Mediates Fibroblast Growth Factor-Inducible 14 Signaling

Fn14

FGR (Gene Name)

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