Sirtuin 7 Inhibitor Attenuates Colonic Mucosal Immune Activation in Mice—Potential Therapeutic Target in Inflammatory Bowel Disease

Kim, Sang Hyun; Byun, Junhyoung; Jung, Semyung; Kim, Byoung Jae; Lee, Kang Won; Jeon, Han Jo; Lee, Jae Min; Choi, Hyuk Soon; Lee, Jae Min; Choi, Hyuk Soon; Kim, Eun Sun; Chun, Hoon Jai; Keum, Bora; Kim, Tae Hoon

doi:10.3390/biomedicines10112693

Cited by 4 publications

(3 citation statements)

References 36 publications

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“…Given that SIRT7 is involved in various immune-mediated inflammatory responses (including the NF-kB inflammatory pathway), SIRT7 may, therefore, be closely associated with intestinal immune-mediated inflammatory responses, such as inflammatory bowel disease (IBD). Kim et al showed that SIRT7 attenuated colonic mucosal inflammation in mice (42). Overall, there are many studies on the mechanisms of SIRTs family involvement in inflammation, especially involving NF-kB, TNF-a, NLRP3, and MAPK-related pathways.…”

Section: Relationship Between Sirts and Immune Inflammationmentioning

confidence: 99%

Sirtuin family in autoimmune diseases

Tao

Jin

et al. 2023

Front. Immunol.

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In recent years, epigenetic modifications have been widely researched. As humans age, environmental and genetic factors may drive inflammation and immune responses by influencing the epigenome, which can lead to abnormal autoimmune responses in the body. Currently, an increasing number of studies have emphasized the important role of epigenetic modification in the progression of autoimmune diseases. Sirtuins (SIRTs) are class III nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases and SIRT-mediated deacetylation is an important epigenetic alteration. The SIRT family comprises seven protein members (namely, SIRT1–7). While the catalytic core domain contains amino acid residues that have remained stable throughout the entire evolutionary process, the N- and C-terminal regions are structurally divergent and contribute to differences in subcellular localization, enzymatic activity and substrate specificity. SIRT1 and SIRT2 are localized in the nucleus and cytoplasm. SIRT3, SIRT4, and SIRT5 are mitochondrial, and SIRT6 and SIRT7 are predominantly found in the nucleus. SIRTs are key regulators of various physiological processes such as cellular differentiation, apoptosis, metabolism, ageing, immune response, oxidative stress, and mitochondrial function. We discuss the association between SIRTs and common autoimmune diseases to facilitate the development of more effective therapeutic strategies.

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Section: Relationship Between Sirts and Immune Inflammationmentioning

confidence: 99%

Sirtuin family in autoimmune diseases

Tao

Jin

et al. 2023

Front. Immunol.

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“…Присутствие LPS из Bacteroides fragilis в сыворотке крови вносит вклад в воспаление при ВЗК [da Silva et al, 2023]. Недостатками препаратов первой линии терапии при ВЗК, включая производные 5-аминосалициловой кислоты, глюкокортикостероиды, иммуносупрессоры, генно-инженерные биологические препараты, являются побочные эффекты, в том числе системная иммуносупрессия, индивидуальная непереносимость, рефрактерность более чем у 30% пациентов [Kim et al, 2022]. В связи с этим, востребованной становится разработка новых, обоснованных с патогенетических позиций и безопасных лекарственных средств преимущественно локального действия с активными веществами эндогенного или растительного происхождения.…”

Section: Introductionunclassified

Melatonin as a promising factor in correction of the intestinal microbiome in inflammatory bowel diseases

Osikov,

Grechishkin,

Shishkova

et al. 2023

Вест. ПГУ. Биол.

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Inflammatory bowel diseases (IBD) include ulcerative colitis and Crohn's disease. The etiology and pathogenesis of IBD remain unclear, the most common hypothesis being that an abnormal immune response against the gut microbiome is triggered by environmental factors in genetically predisposed individuals. The disadvantages of first-line therapy for IBD are the occurrence of side effects in more than 30% of patients. In this regard, the development of new safe drugs that act mainly locally is relevant. The aim of the work is to analyze current data on the mechanisms of action, effects on the intestinal microbiome of melatonin in the context of possible use in IBD. Melatonin (MT) is a biologically active substance, synthesized in the body from tryptophan, and realizes its effects through MT-dependent and MT-independent receptors located in the cell membrane and nucleus. MT is involved in the regulation of circadian rhythms, has antioxidant and immunomodulatory effects. In experimental modeling of IBD and in clinical conditions, MT reduces the severity of the inflammatory process in the wall of the colon by interrupting the processes of lipid peroxidation and inactivation of free radicals, as well as by acting through specific receptors on the function of blood cells of lymphoid organs. MT in IBD leads to a qualitative and quantitative change in the intestinal microbiome, elimination of signs of dysbiosis, an increase in the number of short-chain fatty acid producers - Actinomycetota (Actinobacteria) and a decrease in the number of bacteria that increase the permeability of the intestinal barrier - Bacteroidota (Bacteroidetes). Presumably, MT has a bacteriostatic effect by binding free iron and acting on the NF-kB and STAT1 signaling pathways, which may be a factor in the correction of colon dysbiosis in IBD. Data on the effect of MT on the composition of the intestinal microbiome are a prerequisite for further preclinical studies and the possible use of melatonin in IBD in clinical practice.

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“…Kim and colleagues evaluated the effectiveness of inhibiting Sirtuin 7 (SIRT7) in a colitis mouse model. The study revealed that inflammatory cytokines and mucosal inflammation extent were suppressed in colitis-induced mice treated with the SIRT7 inhibitor, indicating SIRT7 as a potential novel target for IBD treatment [ 7 ]. Furthermore, high-quality clinical trials were published in the second edition of this Special Issue.…”

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confidence: 99%