ATF6 upregulates XBP1S and inhibits ER stress-mediated apoptosis in osteoarthritis cartilage

Guo, Fengjin; Xiong, Zhangyuan; Lu, Xiaojie; Ye, Mengliang; Han, Xiaofeng; Jiang, Rong

doi:10.1016/j.cellsig.2013.11.018

Cited by 81 publications

(71 citation statements)

References 45 publications

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“…Additionally, in this study, microarray analysis showed that BMSC transplantation can downregulate protein processing in the endoplasmic reticulum pathway, while ATF6 and Bcl-2-associated athanohene (BAG2) were involved in this pathway. A previous study (61) demonstrated that ATF6 transcription differed between an endoplasmic reticulum stress (ERS) state and a no-ERS state. ATF6 upregulates the transcription and expression of XBP1 in the no-ERS state, while ATF6 reduces the transcription and expression of XBP1 in the ERS state.…”

Section: Discussionmentioning

confidence: 99%

Microarray expression profiles of genes in lung tissues of rats subjected to focal cerebral ischemia-induced lung injury following bone marrow-derived mesenchymal stem cell transplantation

Xiong

Zhang

et al. 2016

International Journal of Molecular Medicine

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Ischemia-induced stroke is the most common disease of the nervous system and is associated with a high mortality rate worldwide. Cerebral ischemia may lead to remote organ dysfunction, particular in the lungs, resulting in lung injury. Nowadays, bone marrow-derived mesenchymal stem cells (BMSCs) are widely studied in clinical trials as they may provide an effective solution to the treatment of neurological and cardiac diseases; however, the underlying molecular mechanisms remain unknown. In this study, a model of permanent focal cerebral ischemia-induced lung injury was successfully established and confirmed by neurological evaluation and lung injury scores. We demonstrated that the transplantation of BMSCs (passage 3) via the tail vein into the lung tissues attenuated lung injury. In order to elucidate the underlying molecular mechanisms, we analyzed the gene expression profiles in lung tissues from the rats with focal cerebral ischemia and transplanted with BMSCs using a Gene microarray. Moreover, the Gene Ontology database was employed to determine gene function. We found that the phosphoinositide 3-kinase (PI3K)-AKT signaling pathway, transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF) were downregulated in the BMSC transplantation groups, compared with the control group. These results suggested that BMSC transplantation may attenuate lung injury following focal cerebral ischemia and that this effect is associated with the downregulation of TGF-β, PDGF and the PI3K-AKT pathway.

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Section: Discussionmentioning

confidence: 99%

Microarray expression profiles of genes in lung tissues of rats subjected to focal cerebral ischemia-induced lung injury following bone marrow-derived mesenchymal stem cell transplantation

Xiong

Zhang

et al. 2016

International Journal of Molecular Medicine

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“…In the present study, we found that XBP1u is involved in the basal level expression of HO-1 in cultured ECs and responsible for flow-induced HO-1 up-regulation and that overexpression of XBP1u could induce HO-1 expression. Under ER stress, the activation of ATF6 can trigger XBP1 transcription, leading to the increase of both XBP1u and XBP1s (10, 11, 47). Therefore, a protective role of XBP1u via HO-1 in ER stress may be studied.…”

Section: Discussionmentioning

confidence: 99%

Unspliced X-box-binding Protein 1 (XBP1) Protects Endothelial Cells from Oxidative Stress through Interaction with Histone Deacetylase 3

Martin

Yang

et al. 2014

Journal of Biological Chemistry

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Background: The role of the unspliced XBP1 remains unclear.Results: Disturbed flow concomitantly up-regulates XBP1u and HDAC3, which form a complex with Akt1 and mTOR, leading to Nrf2-mediated HO-1 expression.Conclusion: XBP1u and HDAC3 synergistically exert a protective effect on disturbed flow-induced oxidative stress via regulation of HO-1 expression.Significance: This study provides new insights into the physiological roles of XBP1u and HDAC3.

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“…It is also reported to initiate cell death by activating JNK pathway [47]. In contrast, there is also evidence supporting a prosurvival role of IRE1 α [48, 49]. Elevated intracellular calcium level may also contribute to apoptosis of cells under ER stress [50].…”

Section: Discussionmentioning

confidence: 99%

Baicalein Induces Apoptosis and Autophagy via Endoplasmic Reticulum Stress in Hepatocellular Carcinoma Cells

Wang

Jiang

Chen

et al. 2014

BioMed Research International

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Background. Hepatocellular carcinoma (HCC) remains a disastrous disease and the treatment for HCC is rather limited. Separation and identification of active compounds from traditionally used herbs in HCC treatment may shed light on novel therapeutic drugs for HCC. Methods. Cell viability and colony forming assay were conducted to determine anti-HCC activity. Morphology of cells and activity of caspases were analyzed. Antiapoptotic Bcl-2 family proteins and JNK were also examined. Levels of unfolded protein response (UPR) markers were determined and intracellular calcium was assayed. Small interfering RNAs (siRNAs) were used to investigate the role of UPR and autophagy in baicalein-induced cell death. Results. Among four studied flavonoids, only baicalein exhibited satisfactory inhibition of viability and colony formation of HCC cells within water-soluble concentration. Baicalein induced apoptosis via endoplasmic reticulum (ER) stress, possibly by downregulating prosurvival Bcl-2 family, increasing intracellular calcium, and activating JNK. CHOP was the executor of cell death during baicalein-induced ER stress while eIF2α and IRE1α played protective roles. Protective autophagy was also triggered by baicalein in HCC cells. Conclusion. Baicalein exhibits prominent anti-HCC activity. This flavonoid induces apoptosis and protective autophagy via ER stress. Combination of baicalein and autophagy inhibitors may represent a promising therapy against HCC.

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ATF6 upregulates XBP1S and inhibits ER stress-mediated apoptosis in osteoarthritis cartilage

Cited by 81 publications

References 45 publications

Microarray expression profiles of genes in lung tissues of rats subjected to focal cerebral ischemia-induced lung injury following bone marrow-derived mesenchymal stem cell transplantation

Microarray expression profiles of genes in lung tissues of rats subjected to focal cerebral ischemia-induced lung injury following bone marrow-derived mesenchymal stem cell transplantation

Unspliced X-box-binding Protein 1 (XBP1) Protects Endothelial Cells from Oxidative Stress through Interaction with Histone Deacetylase 3

Baicalein Induces Apoptosis and Autophagy via Endoplasmic Reticulum Stress in Hepatocellular Carcinoma Cells

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