Sirtuins—Novel Regulators of Epigenetic Alterations in Airway Inflammation

Wu, Shunyu; Liu, Huanhai

doi:10.3389/fgene.2022.862577

Cited by 2 publications

(1 citation statement)

References 122 publications

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“…In addition, epigenetic alteration is implied in the occurrence and development of various respiratory diseases. 652 Since SIRTs are NAD-dependent deacetylases, their deacetylation activity via epigenetics might be a new research strategy. However, detailed epigenetic roles of SIRTs in the respiratory system still need to be further explored.…”

Section: Introductionmentioning

confidence: 99%

The sirtuin family in health and disease

Zhang

Chen

et al. 2022

Sig Transduct Target Ther

213

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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

213

View full text Add to dashboard Cite

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Sirt5 affects the metabolic remodeling of eosinophils by negatively regulating the level of succinylation modification of Pkm2 in eosinophilic chronic rhinosinusitis

Wu,

Cai,

Cao

et al. 2024

World j. otorhinolaryngol.-head neck surg.

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ObjectivesThis study aims to investigate the role of Sirt5 in regulating eosinophil maturation and activation, specifically focusing on primary eosinophils in mice at the genetic level. Additionally, the study aims to elucidate the underlying mechanism of Sirt5 in eosinophilic inflammation metabolism and identify potential drug targets for the treatment of chronic sinusitis. The findings of this study will provide new insights and a solid theoretical basis for the development of novel therapeutic strategies for eosinophilic chronic rhinosinusitis (eCRS).MethodsOur study investigated the role of Sirt5 gene expression in both non‐eCRS and eCRS. We examined the correlation between Sirt5 gene expression and disease severity as well as eosinophil infiltration. Additionally, we utilized a mouse model of eCRS to assess the impact of Sirt5 gene deletion on the disease. To further understand the underlying mechanisms, we conducted experiments at the single‐cell level using bone marrow‐derived eosinophils. We validated our findings through in vitro culture of eosinophils and intervention experiments. Through these experiments, we aimed to elucidate how Sirt5 regulates target proteins and reshapes their related metabolic pathways.ResultsThere is a positive correlation between the severity of eCRS and the expression level of Sirt5 in nasal mucosa. Inhibiting Sirt5 expression can effectively alleviate the abnormal activation of eosinophils and the resulting inflammatory response in eCRS‐affected nasal mucosa. Sirt5 exerts its influence on eosinophil metabolism by negatively regulating the succinylation level of pkm2, a critical gene in the amino acid biosynthesis pathway.ConclusionsThe severity of eCRS is closely associated with the expression level of Sirt5. Sirt5 plays a negative regulatory role in the succinylation level of Pkm2 in eosinophils, thereby influencing metabolic remodeling and functional activation in eCRS. Investigating Sirt5 and its downstream metabolic pathways could offer valuable insights into the disease's pathogenesis and facilitate the development of targeted therapeutic strategies. This research holds significant implications for clinical practitioners involved in the diagnosis and treatment of patients with eCRS.

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Sirtuins—Novel Regulators of Epigenetic Alterations in Airway Inflammation

Cited by 2 publications

References 122 publications

The sirtuin family in health and disease

The sirtuin family in health and disease

Sirt5 affects the metabolic remodeling of eosinophils by negatively regulating the level of succinylation modification of Pkm2 in eosinophilic chronic rhinosinusitis

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