Role of the TWEAK/Fn14 pathway in autoimmune diseases

Xu, Wang‐Dong; Zhao, Yi; Liu, Yi

doi:10.1007/s12026-015-8761-y

Cited by 35 publications

(18 citation statements)

References 51 publications

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“…Unlike other inflammatory diseases such as psoriasis or autoimmune diseases [ 85 , 86 ], the circulating level of TWEAK is not elevated in patients with AD nor do they correlate with AD severity [ 87 ]. TWEAK expression has been detected not only in lesional AD skin but also in healthy skin [ 87 ].…”

Section: The Function Of Tweak/fn14 Signals In Admentioning

confidence: 99%

TWEAK/Fn14 Activation Participates in Skin Inflammation

Liu

Xiao

Xia

2017

Mediators of Inflammation

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Tumor necrosis factor- (TNF-) like weak inducer of apoptosis (TWEAK) participates in multiple biological activities via binding to its sole receptor—fibroblast growth factor-inducible 14 (Fn14). The TWEAK/Fn14 signaling pathway is activated in skin inflammation and modulates the inflammatory responses of keratinocytes by activating nuclear factor-κB signals and enhancing the production of several cytokines, including interleukins, monocyte chemotactic protein-1, RANTES (regulated on activation, normal T cell expressed and secreted), and interferon gamma-induced protein 10. Mild or transient TWEAK/Fn14 activation contributes to tissular repair and regeneration while excessive or persistent TWEAK/Fn14 signals may lead to severe inflammatory infiltration and tissue damage. TWEAK also regulates cell fate of keratinocytes, involving the function of Fn14-TNF receptor-associated factor-TNF receptor axis. By recruiting inflammatory cells, promoting cytokine production, and regulating cell fate, TWEAK/Fn14 activation plays a pivotal role in the pathogenesis of various skin disorders, such as psoriasis, atopic dermatitis, cutaneous vasculitis, human papillomavirus infection and related skin tumors, and cutaneous autoimmune diseases. Therefore, the TWEAK/Fn14 pathway may be a potential target for the development of novel therapeutics for skin inflammatory diseases.

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Section: The Function Of Tweak/fn14 Signals In Admentioning

confidence: 99%

TWEAK/Fn14 Activation Participates in Skin Inflammation

Liu

Xiao

Xia

2017

Mediators of Inflammation

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“…The expression of TWEAK and Fn14 is up-regulated in a number of human skin diseases (Cheng et al, 2015(Cheng et al, , 2016Doerner et al, 2015;Zimmermann et al, 2011). In recent years, an increasing amount of evidence has implicated the participation of TWEAK in the pathogenesis of a wide variety of autoimmune diseases that include systemic lupus erythematosus, rheumatoid arthritis, polymyositis, and dermatomyositis (Burkly et al, 2011;Peng et al, 2014;Xu et al, 2016). Moreover, TWEAK/Fn14 blockade, using genetically modified mice or neutralizing antibodies, ameliorated experimental autoimmune diseases, such as cutaneous or neuropsychiatric lupus erythematosus and nephrotoxic serum nephritis (Doerner et al, 2015;Wen et al, 2013;Xia et al, 2012Xia et al, , 2015.…”

Section: Introductionmentioning

confidence: 99%

TWEAK/Fn14 Activation Contributes to the Pathogenesis of Bullous Pemphigoid

Liu

Peng

et al. 2017

Journal of Investigative Dermatology

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TWEAK participates in various cellular effects by engaging its receptor of Fn14. Increased levels of soluble TWEAK are associated with systemic autoimmunity in patients with lupus erythematosus, rheumatoid arthritis, or dermatomyositis. However, the role of TWEAK in bullous pemphigoid (BP) remains unknown. In this study, we found an elevated serum level of TWEAK and a positive correlation between serum TWEAK and anti-BP180 antibodies. Immunohistochemistry showed strong TWEAK and Fn14 expression and implied an opposite relationship between the TWEAK and BP180 expression in skin samples from BP patients. In vitro TWEAK stimuli reduced BP180 expression in HaCaT cells and inhibited the adhesion of cells to the culture dish. Consistently, the transfection of Fn14 small interfering RNA preserved BP180 and protected cells from losing adherence. Moreover, such effect of TWEAK correlated with activation of the extracellular signal-regulated kinase and NF-κB pathways and downstream ADAMs. By silencing ADAM17 with small interfering RNA, we showed that ADAM17 participated in TWEAK-induced BP180 loss. Therefore, TWEAK may contribute to the pathogenesis of BP by reducing BP180 expression and cellular adherence, involving the activation of ERK and NF-κB pathways. TWEAK may serve as a biomarker or therapeutic target of BP.

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“…TWEAK, a member of the TNF superfamily, is expressed in multiple tissues. The many biological functions of TWEAK include the regulation of cell apoptosis and necrosis, proliferation, migration, and differentiation; in addition, this protein can trigger angiogenesis and induce the expression of inflammatory cytokines (Xu, Zhao, & Liu, ). TWEAK has only one receptor, fibroblast growth factor‐inducible 14 (Fn14), which is a type I transmembrane protein, and TWEAK is the only ligand of Fn14.…”

Section: Discussionmentioning

confidence: 99%

Hepatic progenitor cell activation is induced by the depletion of the gut microbiome in mice

Wang

Sun

et al. 2019

MicrobiologyOpen

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The homeostasis of the gut microbiome is crucial for human health and for liver function. However, it has not been established whether the gut microbiome influence hepatic progenitor cells (HPCs). HPCs are capable of self‐renewal and differentiate into hepatocytes and cholangiocytes; however, HPCs are normally quiescent and are rare in adults. After sustained liver damage, a ductular reaction occurs, and the number of HPCs is substantially increased. Here, we administered five broad‐spectrum antibiotics for 14 days to deplete the gut microbiomes of male C57BL/6 mice, and we measured the plasma aminotransferases and other biochemical indices. The expression levels of two HPC markers, SRY‐related high mobility group‐box gene 9 (Sox9) and cytokeratin (CK), were also measured. The plasma aminotransferase activities were not affected, but the triglyceride, lactate dehydrogenase, low‐density lipoprotein, and high‐density lipoprotein concentrations were significantly altered; this suggests that liver function is affected by the composition of the gut microbiome. The mRNA expression of Sox9 was significantly higher in the treated mice than it was in the control mice (p < 0.0001), and a substantial expression of Sox9 and CK was observed around the bile ducts. The mRNA expression levels of proinflammatory factors (interleukin [IL]‐1β, IL‐6, tumor necrosis factor [TNF]‐α, and TNF‐like weak inducer of apoptosis [Tweak]) were also significantly higher in the antibiotic‐treated mice than the levels in the control mice. These data imply that the depletion of the gut microbiome leads to liver damage, negatively impacts the hepatic metabolism and function, and activates HPCs. However, the underlying mechanisms remain to be determined.

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Role of the TWEAK/Fn14 pathway in autoimmune diseases

Cited by 35 publications

References 51 publications

TWEAK/Fn14 Activation Participates in Skin Inflammation

TWEAK/Fn14 Activation Participates in Skin Inflammation

TWEAK/Fn14 Activation Contributes to the Pathogenesis of Bullous Pemphigoid

Hepatic progenitor cell activation is induced by the depletion of the gut microbiome in mice

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