SIRT1 is regulated by a PPARγ–SIRT1 negative feedback loop associated with senescence

Han, Limin; Zhou, Rui; Niu, Jing; McNutt, Michael A.; Wang, Pan; Tong, Tanjun

doi:10.1093/nar/gkq609

Cited by 194 publications

(146 citation statements)

References 32 publications

(38 reference statements)

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“…The inducible Sirt1 Ϫ/Ϫ mice used in our studies may mimic some of the responses to PM 2.5 exposure in aging. [21][22][23][24][25][26] Our study suggests that decreased Sirt1 expression in the elderly could be a potential risk factor for PM-induced coagulation and inflammation.…”

Section: Sirt1 Controls Lung Inflammation and Coagulation 2427mentioning

confidence: 68%

“…6,33 Interestingly, Sirt1 expression is down-regulated in multiple organs during aging. 24 In Sirt1 flox/flox /Cre-ERT mice generated in the current study, Cre-ERT fusion protein expression is controlled by a human ubiquitin C (UBC) promoter, which drives tamoxifeninducible and Cre-mediated Sirt1 deletion ubiquitously. The inducible Sirt1 Ϫ/Ϫ mice used in our studies may mimic some of the responses to PM 2.5 exposure in aging.…”

Section: Sirt1 Controls Lung Inflammation and Coagulation 2427mentioning

confidence: 97%

“…[21][22][23][24][25][26] NF-B, a transcription factor that regulates inflammatory responses, is an endogenous substrate for Sirt1. [27][28][29][30] It has been reported that Sirt1 deacetylates NF-B, thereby inhibiting its activity in several in vitro and in vivo systems.…”

Section: Introductionmentioning

confidence: 99%

“…[21][22][23][24][25][26] Interestingly, Sirt1 expression in the lung is reduced in the elderly who are known to be particularly susceptible to PM-induced cardiopulmonary mortality. 24,33 In this study, we investigated the role of Sirt1 in PM-induced lung coagulation. …”

mentioning

confidence: 99%

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Sirt1 protects against thrombomodulin down-regulation and lung coagulation after particulate matter exposure

Liu

Liang

et al. 2012

Blood

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Exposure to ambient particulate matter (PM) air pollution has been reported to trigger inflammation and thrombosis. However, molecular mechanisms underlying the modulation of coagulation pathways in PM-induced thrombosis remain largely unknown. We report here that Sirt1, a member of class III histone deacetylase, controls lung inflammation and coagulation after PM exposure. Sirt1 knock-out mice exhibited aggravated lung vascular leakage and inflammation after PM exposure, which was correlated with increased NF-B acetylation and activation. Furthermore, Sirt1 knock-out mice were highly susceptible to PM-induced lung coagulation as demonstrated by increased fibrin formation. The increased fibrin formation was associated with reduced tissue factor pathway inhibitor (TFPI) expression and increased plasminogen activator inhibitor-1 (PAI-1) activity in the lungs, thus favoring elevated coagulation and disrupted fibrinolysis responses. Thrombomodulin (TM), a central player of the anticoagulant protein C system, is regulated by Kruppel-like factor 2 (KLF2) at the transcriptional level. IntroductionExposure to ambient particulate matter (PM) air pollution has been associated with impaired pulmonary function and increased cardiovascular disease-related mortality including inflammation and thrombosis. 1-5 Acute exposure to increased ambient fine particulate matter Ͻ 2.5 m in diameter (PM 2.5 ) was estimated to cause the premature deaths of tens of thousands of people each year in the United States. 6 Urban particulate matter (UPM) PM 2.5, one of the major air pollutants closely monitored by the US Environmental Protection Agency (EPA), is a complex mixture of substances that are directly emitted into the air from dust, soot, smoke, and combustion. 6 To protect public health, the EPA issued the current 24-hour PM 2.5 standard at 35 g/m 3 . 6 Despite the enormous health problems caused by PM 2.5 exposure, there have been few studies performed to explore the molecular mechanisms of PM 2.5 -induced lung vascular dysfunction. PM 2.5 can reach deep in the lung to the small airway and alveoli, 6 and directly cause lung inflammation and injury. [7][8][9][10][11][12][13] The pulmonary complications may lead to detrimental effects on other organs, particularly cardiovascular dysfunction such as systemic microvascular dysfunction and thrombosis. 1,2,4,5,13 A recent study demonstrated that short-term UPM exposure triggered the activation of primary hemostasis in healthy mice, with no substantial secondary hemostasis activation, leading to arterial but not venous thrombosis. 5 Whereas another study showed that short-term UPM exposure may cause activation of coagulation responses and fibrin formation in the lung. 14 Tissue factor pathway inhibitor (TFPI) and plasminogen activator inhibitor-1 (PAI-1) play important roles in coagulation and fibrinolysis cascades, respectively. TFPI is an inhibitor of tissue factor (TF)-mediated coagulation responses. 15 PAI-1, on the other hand, is a major regulator of fibrinolysis, which functions by in...

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Section: Sirt1 Controls Lung Inflammation and Coagulation 2427mentioning

confidence: 68%

Section: Sirt1 Controls Lung Inflammation and Coagulation 2427mentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Sirt1 protects against thrombomodulin down-regulation and lung coagulation after particulate matter exposure

Liu

Liang

et al. 2012

Blood

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“…The widely used natural sirtuin activator resveratrol has been shown to bind and activate PPARα directly [195]. SIRT1 also reverses the p300-dependent acetylation of PPARγ [72] and seems to inhibit its transactivation function [156]. PPARα, PPARγ, and PPARδ agonists were able to increase SIRT1 expression [35,100,213]; PPARα activation also blocked SIRT1 export from the nucleus [213].…”

Section: Transcriptional and Post-transcriptional Regulators As Sirtumentioning

confidence: 99%

Sirtuins and their interactions with transcription factors and poly(ADP-ribose) polymerases

Jęśko¹,

Strosznajder²

2016

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A b s t r a c tSirtuins vast number of targets in many cellular compartments, and some display additional enzymatic activities including mono(ADP-ribosyl)ation. SIRTs interact with multiple signalling proteins, transcription factors and enzymes including p53, FOXOs (forkhead box subgroup O), PPARs (peroxisome proliferator-activated receptors), NF-κB, and DNA-PK (DNA-dependent protein kinase). Sirtuins also interact extensively with the family of poly(ADPribose) polymerases (PARPs), a crucial and widespread class of NAD

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Progranulin deficiency suppresses allergic asthma and enhances efferocytosis via PPAR‐γ/MFG‐E8 regulation in macrophages

Huang

Weng

Yao

et al. 2023

Immunity Inflam & Disease

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Efferocytosis can resolve airway inflammation and enhance airway tolerance in allergic asthma. While previous work has reported that progranulin (PGRN) regulated macrophage efferocytosis, but it is unclear whether PGRN‐mediated efferocytosis is associated with asthma. Here, we found that in an ovalbumin (OVA)‐induced allergic asthma model, the airway inflammation was suppressed and the apoptosis in lung tissues was ameliorated in PGRN‐deficient mice. In contrast, PGRN knockdown in human bronchial epithelial cells increased apoptosis in vitro. Furthermore, PGRN‐deficient macrophages had significantly stronger efferocytosis ability than wild type (WT) macrophages both in vitro and in vivo. PGRN‐deficient peritoneal macrophages (PMs) exhibited increased expression of genes associated with efferocytosis including milk fat globule‐epidermal growth factor 8 (MFG‐E8), peroxisome proliferator‐activated receptor gamma (PPAR‐γ) and sirtuin1 (SIRT1) and increased capacity to produce the anti‐inflammatory mediator interleukin (IL)‐10 during efferocytosis. GW9662, the inhibitor of PPAR‐γ, abolished increased efferocytosis and MFG‐E8 expression in PGRN‐deficient PMs suggesting that PGRN deficiency enhanced MFG‐E8‐mediated efferocytosis through PPAR‐γ. Correspondingly, efferocytosis genes were increased in the lungs of OVA‐induced PGRN‐deficient mice. GW9662 treatment reduced MFG‐E8 expression but did not significantly affect airway inflammation. Our results demonstrated that PGRN deficiency enhanced efferocytosis via the PPAR‐γ/MFG‐E8 pathway and this may be one of the reasons PGRN deficiency results in inhibition of airway inflammation in allergic asthma.

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SIRT1 is regulated by a PPARγ–SIRT1 negative feedback loop associated with senescence

Cited by 194 publications

References 32 publications

Sirt1 protects against thrombomodulin down-regulation and lung coagulation after particulate matter exposure

Sirt1 protects against thrombomodulin down-regulation and lung coagulation after particulate matter exposure

Sirtuins and their interactions with transcription factors and poly(ADP-ribose) polymerases

Progranulin deficiency suppresses allergic asthma and enhances efferocytosis via PPAR‐γ/MFG‐E8 regulation in macrophages

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