Protective Effects of SIRT6 Overexpression against DSS-Induced Colitis in Mice

Xu, Kang; Guo, Yanfei; Lü, Ping; Qiu, Ying; Liu, Qingfei; Li, Zhongchi; Wang, Zhao

doi:10.3390/cells9061513

Cited by 22 publications

(19 citation statements)

References 36 publications

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“…Results of a previous study demonstrated that the expression of JNK in the MAPK signaling family is increased in intestinal ischemic tissues (27). Moreover, activation of TAK1-dependent NF-κB and proto-oncogene c-Jun is associated with the occurrence of intestinal inflammation and, in the case of dextran sodium sulfate-induced enteritis, the expression levels of TAK1 are significantly increased (28). These findings are consistent with those of the present study.…”

Section: Discussionsupporting

confidence: 92%

Intestinal ischemia‑reperfusion induces the release of IL‑17A to regulate cell inflammation, apoptosis and barrier damage

et al. 2021

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Intestinal ischemia-reperfusion (I/R) injury promotes the release of IL-17A, and previous studies have indicated that TGF-β activated kinase 1 (TAK1) is an important signaling molecule in the regulatory function of IL-17A. The present study aimed to explore the potential effects of IL-17A release in intestinal I/R injury, and to investigate the underlying regulatory mechanisms. Initially, the expression levels of TAK1 and JNK in a hypoxia/reoxygenation model were determined, and the effects of TAK1-knockdown on JNK phosphorylation and the viability, inflammation, apoptosis and barrier function of Caco-2 cells were assessed using Cell Counting Kit-8, reverse transcription-quantitative PCR, TUNEL and transepithelial electrical resistance assays, respectively. Subsequently, an antibody targeting IL-17A was used, and the effects of the IL-17A antibody on the expression levels of TAK1 as well as cell viability, inflammation, apoptosis and barrier function were determined. The results of the present study demonstrated that TAK1-knockdown markedly reduced JNK phosphorylation and improved the levels of cell viability, inflammation, apoptosis and barrier function via the MAPK signaling pathway. In addition, treatment with the IL-17A antibody inhibited the expression of TAK1, and reversed the aforementioned effects of TAK1 on Caco-2 cells. In conclusion, intestinal I/R induces the release of IL-17A to regulate cell viability, inflammation, apoptosis and barrier damage via the TAK1/MAPK signaling pathway.

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Section: Discussionsupporting

confidence: 92%

Intestinal ischemia‑reperfusion induces the release of IL‑17A to regulate cell inflammation, apoptosis and barrier damage

et al. 2021

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“…Unfortunately, we did not have enough evidence to demonstrate how SIRT6 regulated p‐IκBα. It has been reported that SIRT6 may regulate phosphorylation and activation of TAK1 to inhibit NF‐κB signal‐related proteins 53 . Li et al demonstrated that SIRT6 interacted with the DNA binding domain of p65, and that this interaction decreased the occupancy of p65 at the NF‐κB target gene promoter and downregulated expression levels of p‐IκBα 54 .…”

Section: Discussionmentioning

confidence: 99%

Icariin‐induced inhibition of SIRT6/NF‐κB triggers redox mediated apoptosis and enhances anti‐tumor immunity in triple‐negative breast cancer

et al. 2020

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Abnormal activation of the nuclear factor‐kappa B (NF‐κB) signaling pathway is closely implicated in triple‐negative breast cancer growth, metastasis, and tumor immune escape. In this study, the anti‐cancer effects of icariin, a natural flavonol glycoside, toward breast cancer cells and the underlying mechanisms were investigated. This investigation showed that icariin selectively inhibited proliferation and triggered apoptosis in breast cancer cells in a concentration‐ and time‐dependent manner, but exhibited little cytotoxicity in normal breast cells. Moreover, icariin induced cell apoptosis via a mitochondria‐mediated pathway, as indicated by the upregulated ratio of Bax/Bcl‐2 and reactive oxygen species induction. Importantly, icariin impaired the activation of the NF‐κB/EMT pathway, as evidenced by upregulation of SIRT6, resulting in inhibition of migration and invasion of breast cancer cells. Additionally, oss‐128167, an inhibitor of SIRT6, dramatically attenuated anti‐migration and anti‐invasion effects of icariin. Transcriptomic analysis verified that impairment of NF‐κB led to the selective function of icariin in breast cancer cells. Notably, icariin exhibited a significant tumor growth inhibition and anti‐pulmonary metastasis effect in a tumor mouse model of MDA‐MB‐231 and 4T1 cells by regulating the tumor immunosuppressive microenvironment. Together, these results showed that icariin could effectively trigger apoptosis and inhibit the migration of breast cancer cells via the SIRT6/NF‐κB signaling pathway, suggesting that icariin might serve as a potential candidate drug for the treatment of breast cancer.

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“…Recently, a study showed that the upregulation of SIRT6 lowered the levels of inflammatory factors TNF-a, IL-1β, and IL-6 in LPS-injured PC12 cells ( Zhaohuia and Shuiua 2020 ). SIRT6 transgenic mice showed lower levels of pro-inflammatory cytokines like TNF-a, IL-1β, and IL-6 in the dextran sulfate sodium salt (DSS)-induced colitis model than normal mice ( Xu et al, 2020 ). In addition, previous studies have reported that the SIRT6 activator UBCS039 could effectively upregulate SIRT6 and inhibit the activation of macrophages ( Zou et al, 2021 ; Wang et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

SIRT6 Activator UBCS039 Inhibits Thioacetamide-Induced Hepatic Injury In Vitro and In Vivo

Jiao

Zhang

et al. 2022

Front. Pharmacol.

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SIRT6 has been reported to have multiple functions in inflammation and metabolism. In the present study, we explored the regulatory effects and mechanisms of SIRT6 in thioacetamide (TAA)-induced mice acute liver failure (ALF) models. The SIRT6 activator UBCS039 was used in this animal and cell experiments. We observed that UBCS039 ameliorated liver damage, including inflammatory responses and oxidative stress. Further study of mechanisms showed that the upregulation of SIRT6 inhibited the inflammation reaction by suppressing the nuclear factor-κB (NF-κB) pathway in the TAA-induced ALF mice model and lipopolysaccharide-stimulated macrophages. In addition, the upregulation of SIRT6 alleviated oxidative stress damage in hepatocytes by regulating the Nrf2/HO-1 pathway. These findings demonstrate that pharmacologic activator of SIRT6 could be a promising target for ALF.

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Protective Effects of SIRT6 Overexpression against DSS-Induced Colitis in Mice

Cited by 22 publications

References 36 publications

Intestinal ischemia‑reperfusion induces the release of IL‑17A to regulate cell inflammation, apoptosis and barrier damage

Intestinal ischemia‑reperfusion induces the release of IL‑17A to regulate cell inflammation, apoptosis and barrier damage

Icariin‐induced inhibition of SIRT6/NF‐κB triggers redox mediated apoptosis and enhances anti‐tumor immunity in triple‐negative breast cancer

SIRT6 Activator UBCS039 Inhibits Thioacetamide-Induced Hepatic Injury In Vitro and In Vivo

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