Novel transcript variants of TRAIL show different activities in activation of NF-κB and apoptosis

Wang, Pingzhang; Lu, Yan; Li, Changqing; Li, Na; Yu, Peng; Ma, Dalong

doi:10.1016/j.lfs.2011.09.003

Cited by 9 publications

(4 citation statements)

References 29 publications

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“…Recently, seven alternatively spliced TRAIL truncated variants were identified that were incapable of potentiating apoptosis: AK, E2, E3, E4, DA, BX424 and BX439 85 . All of these isoforms contain common N-terminal sequences and possess the transmembrane helix but vary in the C-terminal region.…”

Section: Regulation Of the Human Trail Genementioning

confidence: 99%

Regulation of the human TRAIL gene

Allen

El‐Deiry

2012

Cancer Biology & Therapy

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TRAIL is a member of the TNF superfamily that induces tumor-selective cell death by engaging the pro-apoptotic death receptors DR4 and DR5. The antitumor potential of the TRAIL pathway has been targeted by several therapeutic approaches including recombinant TRAIL and TRAIL-receptor agonist antibodies among others. Interest in sensitizing tumor cells to TRAIL-mediated apoptosis has driven investigations of TRAIL-receptor gene regulation, though regulation of the TRAIL gene has been less studied. Physiologically, TRAIL serves as a pro-apoptotic effector molecule in the immune surveillance of cancer that is conditionally expressed by immune cells upon stimulation via an interferon-response element that was identified in early studies of the TRAIL gene promoter. Here, we map the TRAIL gene promoter and review studies of TRAIL gene regulation that involve several modalities of gene regulation including transcription factors, epigenetics, single-nucleotide polymorphisms and functionally distinct isoforms.

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Section: Regulation Of the Human Trail Genementioning

confidence: 99%

Regulation of the human TRAIL gene

Allen

El‐Deiry

2012

Cancer Biology & Therapy

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“…TNF-related apoptosis-inducing ligand (TRAIL; Apo2L) is a type II transmembrane protein whose transcripts are detected in a variety of human tissues, most predominantly in spleen, lung, and prostate (Wiley et al, 1995). They can be alternatively spliced to produce several different isoforms (Wang et al, 2011). There are four membrane TRAIL receptors, DR4 (death receptor 4, TRAIL-R1; Pan et al, 1997b), DR5 (TRAIL-R2; MacFarlane et al, 1997; Pan et al, 1997b; Screaton et al, 1997; Walczak et al, 1997), DcR1 (Decoy Receptor 1, TRAIL-R3; Degli-Esposti et al, 1997b; Pan et al, 1997a; LeBlanc and Ashkenazi, 2003), DcR2 (TRAIL-R4; Degli-Esposti et al, 1997a; Marsters et al, 1997; Pan et al, 1998), and the soluble protein OPG (osteoprotegerin) (Emery et al, 1998).…”

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confidence: 99%

Inhibition of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) reverses experimental pulmonary hypertension

Hameed

Arnold

Chamberlain

et al. 2012

Journal of Experimental Medicine

116

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“…TRAIL signalling is complicated; amplified with the identification of alternatively spliced variants [32], [33], and multifaceted mechanisms involving 5 receptors in humans. TRAIL also has the ability to promote cell survival, proliferation and differentiation via activation of NFκB, mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK) and phosphatidylinositide 3-kinase (PI3K)-dependent pathways (reviewed in [6], [7]).…”

Section: Discussionmentioning

confidence: 99%

TRAIL Deficiency Contributes to Diabetic Nephropathy in Fat-Fed ApoE-/- Mice

2014

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BackgroundWe recently demonstrated that TNF-related apoptosis-inducing ligand (TRAIL) is protective of diet-induced diabetes in mice. While TRAIL has been implicated in chronic kidney disease, its role in vivo in diabetic nephropathy is not clear. The present study investigated the role of TRAIL in the pathogenesis of diabetic nephropathy using TRAIL-/-ApoE-/- mice.MethodsTRAIL-/-ApoE-/- and ApoE-/- mice were fed a high fat diet for 20 w. Plasma glucose and insulin levels were assessed over 0, 5, 8 and 20 w. At 20 w, markers of kidney function including creatinine, phosphate, calcium and cystatin C were measured. Changes in mRNA expression of MMPs, TIMP-1, IL-1β and IL-18 were assessed in the kidney. Functional and histological changes in kidneys were examined. Glucose and insulin tolerance tests were performed.ResultsTRAIL-/-ApoE-/- mice had significantly increased urine protein, urine protein:creatinine ratio, plasma phosphorous, and plasma cystatin C, with accelerated nephropathy. Histologically, increased extracellular matrix, mesangial expansion and mesangial cell proliferation in the glomeruli were observed. Moreover, TRAIL-/-ApoE-/- kidneys displayed loss of the brush border and disorganisation of tubular epithelium, with increased fibrosis. TRAIL-deficient kidneys also had increased expression of MMPs, TIMP-1, PAI-1, IL-1β and IL-18, markers of renal injury and inflammation. Compared with ApoE-/- mice, TRAIL-/-ApoE-/- mice displayed insulin resistance and type-2 diabetic features with reduced renal insulin-receptor expression.ConclusionsHere, we show that TRAIL-deficiency in ApoE-/- mice exacerbates nephropathy and insulin resistance. Understanding TRAIL signalling in kidney disease and diabetes, may therefore lead to novel strategies for the treatment of diabetic nephropathy.

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Novel transcript variants of TRAIL show different activities in activation of NF-κB and apoptosis

Cited by 9 publications

References 29 publications

Regulation of the human TRAIL gene

Regulation of the human TRAIL gene

Inhibition of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) reverses experimental pulmonary hypertension

TRAIL Deficiency Contributes to Diabetic Nephropathy in Fat-Fed ApoE-/- Mice

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