TRIB3 alters endoplasmic reticulum stress-induced β-cell apoptosis via the NF-κB pathway

Ni, Fang; Zhang, Wenjian; Xu, Shiqing; Lin, Haiyan; Wang, Zai; Liu, Honglin; Fang, Qing; Li, Chenghui; Peng, Liang; Lou, Jinning

doi:10.1016/j.metabol.2014.03.003

Cited by 50 publications

(37 citation statements)

References 34 publications

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“…This view was supported by several studies showing increased activation of ER stress sensors and downstream effectors and target genes in different in vitro and in vivo models in addition to human T2D (reviewed in Bensellam et al 2012b). Furthermore, ablation of the ISR gene Ddit3 in different animal models of diabetes has been shown to be protective (Oyadomari et al 2002, Song et al 2008, while overexpression of Trib3 altered glucose tolerance and GSIS and increased β-cell apoptosis (Qian et al 2008, Liew et al 2010, Fang et al 2014. Moreover, adenovirus-mediated overexpression of Atf6 in INS1 cells was associated with altered GSIS and reduced expression of insulin, Pdx1 and Mafa (Seo et al 2008).…”

Section: Journal Of Endocrinologymentioning

confidence: 99%

Mechanisms of β-cell dedifferentiation in diabetes: recent findings and future research directions

Bensellam

Jonas

Laybutt

2018

Journal of Endocrinology

205

171

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Like all the cells of an organism, pancreatic β-cells originate from embryonic stem cells through a complex cellular process termed differentiation. Differentiation involves the coordinated and tightly controlled activation/repression of specific effectors and gene clusters in a time-dependent fashion thereby giving rise to particular morphological and functional cellular features. Interestingly, cellular differentiation is not a unidirectional process. Indeed, growing evidence suggests that under certain conditions, mature β-cells can lose, to various degrees, their differentiated phenotype and cellular identity and regress to a less differentiated or a precursor-like state. This concept is termed dedifferentiation and has been proposed, besides cell death, as a contributing factor to the loss of functional β-cell mass in diabetes. β-cell dedifferentiation involves: (1) the downregulation of β-cell-enriched genes, including key transcription factors, insulin, glucose metabolism genes, protein processing and secretory pathway genes; (2) the concomitant upregulation of genes suppressed or expressed at very low levels in normal β-cells, the β-cell forbidden genes; and (3) the likely upregulation of progenitor cell genes. These alterations lead to phenotypic reconfiguration of β-cells and ultimately defective insulin secretion. While the major role of glucotoxicity in β-cell dedifferentiation is well established, the precise mechanisms involved are still under investigation. This review highlights the identified molecular mechanisms implicated in β-cell dedifferentiation including oxidative stress, endoplasmic reticulum (ER) stress, inflammation and hypoxia. It discusses the role of Foxo1, Myc and inhibitor of differentiation proteins and underscores the emerging role of non-coding RNAs. Finally, it proposes a novel hypothesis of β-cell dedifferentiation as a potential adaptive mechanism to escape cell death under stress conditions.

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Section: Journal Of Endocrinologymentioning

confidence: 99%

Mechanisms of β-cell dedifferentiation in diabetes: recent findings and future research directions

Bensellam

Jonas

Laybutt

2018

Journal of Endocrinology

205

171

View full text Add to dashboard Cite

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“…Notably, TRIB3, a pseudokinase with docking or scaffold functions that can regulate complex signaling pathways, has been shown to negatively feed back on the UPR. It has been reported in neurons and pancreatic β cells to play an important role in eliciting programmed cell death in conditions of chronic ER stress by sensitizing cells to TNF-α-and TRAILinduced apoptosis (61,75).…”

Section: Silencing Of Trib3 In Primary Human Renal Epithelial Cells Rmentioning

confidence: 99%

Uromodulin p.Cys147Trp mutation drives kidney disease by activating ER stress and apoptosis

Johnson

Dang

Marsh

et al. 2017

Journal of Clinical Investigation

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“…However, Our finding that TRIB3 activated phosphorylation of NF‐κB p65 in P. endodontalis LPS‐induced osteoblasts suggested a more complex relationship between TRIB3 and NF‐κB. This would be consistent with the findings that TRIB3 mediated doxycycline induced β‐cell apoptosis through the NF‐κB pathway (Fang et al ., ). Besides directly binding to p65 and inhibiting its phosphorylation, TRIB3 may act through other molecules to promote the phosphorylation of p65.…”

Section: Discussionmentioning

confidence: 97%

TRIB3 mediates the expression of Wnt5a and activation of nuclear factor‐κB in Porphyromonas endodontalis lipopolysaccharide‐treated osteoblasts

Qiu

Guo

et al. 2015

Molecular Oral Microbiology

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Porphyromonas endodontalis lipopolysaccharide (LPS) is considered to be correlated with the progression of bone resorption in periodontal and periapical diseases. Wnt5a has recently been implicated in inflammatory processes, but its role is unclear as a P. endodontalis LPS-induced mediator in osteoblasts. Tribbles homolog 3 (TRIB3) encodes a pseudokinase and has been linked to inflammation in certain situations. Here, we found that P. endodontalis LPS induced Wnt5a expression in a dose- and time-dependent manner and it also upregulated translocation, phosphorylation and transcriptional activity of nuclear factor-κB (NF-κB) in MC3T3-E1 cells. Bay 11-7082 blocked the translocation of NF-κB and Wnt5a expression induced by P. endodontalis LPS. Chromatin immunoprecipitation assay further established that induction of Wnt5a by P. endodontalis LPS was mediated through the NF-κB p65 subunit. Additionally, P. endodontalis LPS increased expression of TRIB3 in osteoblasts after 10 h simulated time. Overexpression of TRIB3 enhanced NF-κB phosphorylation and Wnt5a induction, whereas knockdown of TRIB3 inhibited NF-κB phosphorylation and Wnt5a expression in P. endodontalis LPS-stimulated osteoblasts. These results suggest that P. endodontalis LPS has the ability to promote the expression of Wnt5a in mouse osteoblasts, and this induction is mainly mediated by NF-κB pathway. TRIB3 seems to modulate the sustained expression of Wnt5a in osteoblasts stimulated by P. endodontalis LPS, as well as regulating NF-κB phosphorylation.

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TRIB3 alters endoplasmic reticulum stress-induced β-cell apoptosis via the NF-κB pathway

Cited by 50 publications

References 34 publications

Mechanisms of β-cell dedifferentiation in diabetes: recent findings and future research directions

Mechanisms of β-cell dedifferentiation in diabetes: recent findings and future research directions

Uromodulin p.Cys147Trp mutation drives kidney disease by activating ER stress and apoptosis

TRIB3 mediates the expression of Wnt5a and activation of nuclear factor‐κB in Porphyromonas endodontalis lipopolysaccharide‐treated osteoblasts

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