Krüppel-Like Factor 6 Silencing Prevents Oxidative Stress and Neurological Dysfunction Following Intracerebral Hemorrhage via Sirtuin 5/Nrf2/HO-1 Axis

Sun, Jia; Cai, Jinzhong; Chen, Junhui; Li, Siqiaozhi; Liao, Xin; He, Yijie; Chen, Xudong; Hu, Sean

doi:10.3389/fnagi.2021.646729

Cited by 13 publications

(7 citation statements)

References 30 publications

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“… 187 SIRT5 was upregulated by Krüppel-like factor (KLF) 6 silencing, thereby reducing oxidative stress. 188 Meanwhile, SIRTs target many downstream factors, such as HIF-1α and endothelial nitric oxide synthase (eNOS), and then participate in regulating oxidative stress. Activation of HIF-1α is associated with oxidative stress and can regulate ROS formation through direct or indirect effects.…”

Section: Introductionmentioning

confidence: 99%

The sirtuin family in health and disease

Zhang

Chen

et al. 2022

Sig Transduct Target Ther

223

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Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a potential therapeutic target for different kinds of pathologies including cancer, cardiovascular disease, respiratory disease, and other conditions. Moreover, identification of SIRT modulators and exploring the functions of these different modulators have prompted increased efforts to discover new small molecules, which can modify SIRT activity. Furthermore, several randomized controlled trials have indicated that different interventions might affect the expression of SIRT protein in human samples, and supplementation of SIRT modulators might have diverse impact on physiological function in different participants. In this review, we introduce the history and structure of the SIRT protein family, discuss the molecular mechanisms and biological functions of seven members of the SIRT protein family, elaborate on the regulatory roles of SIRTs in human disease, summarize SIRT inhibitors and activators, and review related clinical studies.

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Section: Introductionmentioning

confidence: 99%

The sirtuin family in health and disease

Zhang

Chen

et al. 2022

Sig Transduct Target Ther

223

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“…HO-1 is a key star molecule in the process of oxidative stress, and the role of HO-1 in inflammatory response has also been widely recognized ( Sun et al, 2021 ; Wang et al, 2021 ; Zhang et al, 2021 ). In recent years, the relationship between HO-1 and immunity has gained some attention ( Yan et al, 2019 ; Van Nguyen et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Butyric Acid Protects Against Renal Ischemia–Reperfusion Injury by Adjusting the Treg/Th17 Balance via HO-1/p-STAT3 Signaling

Chen

Wang

Yang

et al. 2021

Front. Cell Dev. Biol.

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Immune regulation plays a vital role in ischemia–reperfusion injury (IRI). Butyric acid (BA) has immunomodulatory effects in many diseases, but its immunomodulatory effects during renal IRI are still unclear. Our research shows that BA protected against IRI and significantly improved renal IRI in vivo. In vitro studies showed that BA inhibits Th17 cell differentiation and induces Treg cell differentiation. Mechanism studies have shown that heme oxygenase 1 (HO-1)/STAT3 signaling pathway was involved in the inhibitory effect of BA on Th17 cell differentiation. HO-1 inhibitors can significantly rescue the BA-mediated inhibition of Th17 cell differentiation. We confirmed that BA promotes the differentiation of Th17 cells into Treg cells by regulating the pathway and reduces renal IRI.

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“… 25 Furthermore, Sun et al have clarified that the depletion of KLF6 could prevent oxidative stress in intracerebral hemorrhage rats. 26 However, the role of KLF6 in inflammation, apoptosis and oxidative stress in COPD has not been reported yet. In the present study, KLF6 interference was discovered to inhibit cellular inflammation, repress cell apoptosis and suppress oxidative stress in CSE-induced BEAS-2B cells.…”

Section: Discussionmentioning

confidence: 99%

Silencing KLF6 Alleviates Cigarette Smoke Extract-Induced Mitochondrial Dysfunction in Bronchial Epithelial Cells by SIRT4 Upregulation

Wan,

Wang,

Cui

et al. 2024

COPD

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Background The incidence of chronic obstructive pulmonary disease (COPD) is increasing year by year. Kruppel-like factor 6 (KLF6) plays an important role in inflammatory diseases. However, the regulatory role of KLF6 in COPD has not been reported so far. Methods The viability of human bronchial epithelial cells BEAS-2B induced by cigarette smoke extract (CSE) was detected by CCK-8 assay. The protein expression of KLF6 and sirtuin 4 (SIRT4) was appraised with Western blot. RT-qPCR and Western blot were applied to examine the transfection efficacy of sh-KLF6 and Oe-KLF6. Cell apoptosis was detected using flow cytometry. The levels of inflammatory factors IL-6, TNF-α and IL-1β were assessed with ELISA assay. DCFH-DA staining was employed for the detection of ROS activity and the levels of oxidative stress markers SOD, CAT and MDA were estimated with corresponding assay kits. The mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content and Complex I activity were evaluated with JC-1 staining, ATP colorimetric/fluorometric assay kit and Complex I enzyme activity microplate assay kit. With the application of mitochondrial permeability transition pore detection kit, mPTP opening was measured. Luciferase report assay was employed to evaluate the activity of SIRT4 promoter and chromatin immunoprecipitation (ChIP) to verify the binding ability of KLF6 and SIRT4 promoter. Results KLF6 expression was significantly elevated in CSE-induced cells. KLF6 was confirmed to suppress SIRT4 transcription. Interference with KLF6 expression significantly inhibited cell viability damage, cell apoptosis, inflammatory response, oxidative stress and mitochondrial dysfunction in CSE-induced BEAS-2B cells, which were all reversed by SIRT4 overexpression. Conclusion Silencing KLF6 alleviated CSE-induced mitochondrial dysfunction in bronchial epithelial cells by SIRT4 upregulation.

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Krüppel-Like Factor 6 Silencing Prevents Oxidative Stress and Neurological Dysfunction Following Intracerebral Hemorrhage via Sirtuin 5/Nrf2/HO-1 Axis

Cited by 13 publications

References 30 publications

The sirtuin family in health and disease

The sirtuin family in health and disease

Butyric Acid Protects Against Renal Ischemia–Reperfusion Injury by Adjusting the Treg/Th17 Balance via HO-1/p-STAT3 Signaling

Silencing KLF6 Alleviates Cigarette Smoke Extract-Induced Mitochondrial Dysfunction in Bronchial Epithelial Cells by SIRT4 Upregulation

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