SIRT7 deficiency suppresses inflammation, induces EndoMT, and increases vascular permeability in primary pulmonary endothelial cells

Wyman, Anne E.; Nguyen, Trang; Karki, Pratap; Tulapurkar, Mohan E.; Zhang, Chen-Ou; Kim, Jung-Hyun; Feng, Theresa; Dabo, Abdoulaye; Todd, Nevins W.; Luzina, Irina G.; Geraghty, Patrick; Foronjy, Robert; Hasday, Jeffrey D.; Birukova, Anna A.; Atamas, Sergei P.; Birukov, Konstantin G.

doi:10.1038/s41598-020-69236-z

Cited by 23 publications

(17 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Supporting our results, Miyasato, Y. et al, reported that Sirt7 deficient mice, suffering from cisplatin nephrotoxicity, exhibited a reduction in Tnfa, Il1b, Il6, Ccl2 , and Cxcl2 mRNA levels, as well as in F4/F80 positive cells compared to WT mice [ 38 ]. Moreover, it has been reported that Sirt7 deficiency protects against pulmonary endothelium inflammation induced by lipopolysaccharides, an effect that was associated with an increase in TGFβ1 expression and its target genes, driving endothelium-mesenchyme transition to promote cellular repair [ 39 ]. Interestingly, we also found that after IR, the KO-Sirt7 mice had a significant increase in Tgfb1 mRNA levels that was not seen in the WT+IR and HT-Sirt7 groups.…”

Section: Discussionmentioning

confidence: 99%

Sirtuin 7 Deficiency Reduces Inflammation and Tubular Damage Induced by an Episode of Acute Kidney Injury

Sánchez‐Navarro

Martínez‐Rojas

Pérez‐Villalva

et al. 2022

IJMS

View full text Add to dashboard Cite

Acute kidney injury (AKI) is a public health problem worldwide. Sirtuins are a family of seven NAD+-dependent deacylases, Overexpression of Sirtuin 1, 3, and 5 protect against AKI. However, the role of Sirtuin 7 (Sirt7) in AKI is not known. Here, we analyzed how Sirt7 deficient mice (KO-Sirt7) were affected by AKI. As expected, wild-type and Sirt7 heterozygotes mice that underwent renal ischemia/reperfusion (IR) exhibited the characteristic hallmarks of AKI: renal dysfunction, tubular damage, albuminuria, increased oxidative stress, and renal inflammation. In contrast, the KO-Sirt7+IR mice were protected from AKI, exhibiting lesser albuminuria and reduction in urinary biomarkers of tubular damage, despite similar renal dysfunction. The renoprotection in the Sirt7-KO+IR group was associated with reduced kidney weight, minor expression of inflammatory cytokines and less renal infiltration of inflammatory cells. This anti-inflammatory effect was related to diminished p65 expression and in its active phosphorylation, as well as by a reduction in p65 nuclear translocation. Sirt7 deficient mice are protected from AKI, suggesting that this histone deacetylase promotes tubular damage and renal inflammation. Therefore, our findings indicate that Sirt7 inhibitors may be an attractive therapeutic target to reduce NFκB signaling.

show abstract

Section: Discussionmentioning

confidence: 99%

Sirtuin 7 Deficiency Reduces Inflammation and Tubular Damage Induced by an Episode of Acute Kidney Injury

Sánchez‐Navarro

Martínez‐Rojas

Pérez‐Villalva

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Regarding the immune system, SIRT7 silencing reduced lipopolysaccharide (LPS)-induced pro-inflammatory effects and induced an endomesenchymal transition that increased endothelial barrier permeability. All this is a consequence of the suppression of NFκB signaling and the resulting low levels of ICAM1, VCAM1, IL8, IL6, cadherin, and PECAM1, but increases in collagen, αSMA, TGFβR1, and SNAIL [ 105 ]. SIRT7 interacts with RAN and deacetylates it at residue K37, leading to decreased binding between RAN and nuclear export components and, as a consequence, retention of NF-κB p65 in the nucleus [ 106 ].…”

Section: Sirt7 Association With Agingmentioning

confidence: 99%

SIRT7 in the aging process

Lagunas‐Rangel

2022

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Aging is the result of the accumulation of a wide variety of molecular and cellular damage over time. This has been associated with a number of features termed hallmarks of aging, including genomic instability, loss of proteostasis, telomere attrition, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and impaired intercellular communication. On the other hand, sirtuins are enzymes with an important role in aging and life extension, of which humans have seven paralogs (SIRT1 to SIRT7). SIRT7 is the least studied sirtuin to date, but it has been reported to serve important functions, such as promoting ribosomal RNA expression, aiding in DNA damage repair, and regulating chromatin compaction. Several studies have established a close relationship between SIRT7 and age-related processes, but knowledge in this area is still scarce. Therefore, the purpose of this review was to analyze how SIRT7 is associated with each of the hallmarks of aging, as well as with some of age-associated diseases, such as cardiovascular diseases, obesity, osteoporosis, and cancer.

show abstract

“…Claudin-18 deficiency results in alveolar barrier dysfunction and impaired alveologenesis [13,15]. Impaired TJ structure and/or function have also been reported in mice deficient in lymphoblastic leukemia-derived sequence (Lyl)-1, Crumbs (Crb3), and sirtuins (SIRTs) [28][29][30].…”

Section: Genetic Mouse Models Of Tj Proteinsmentioning

confidence: 99%

Tight Junctions, the Epithelial Barrier, and Toll-like Receptor-4 During Lung Injury

et al. 2022

View full text Add to dashboard Cite

Lung epithelium is constantly exposed to the environment and is critically important for the orchestration of initial responses to infectious organisms, toxins, and allergic stimuli, and maintenance of normal gaseous exchange and pulmonary function. The integrity of lung epithelium, fluid balance, and transport of molecules is dictated by the tight junctions (TJs). The TJs are formed between adjacent cells. We have focused on the topic of the TJ structure and function in lung epithelial cells. This review includes a summary of the last twenty years of literature reports published on the disrupted TJs and epithelial barrier in various lung conditions and expression and regulation of specific TJ proteins against pathogenic stimuli. We discuss the molecular signaling and crosstalk among signaling pathways that control the TJ structure and function. The Toll-like receptor-4 (TLR4) recognizes the pathogen-and damage-associated molecular patterns released during lung injury and inflammation and coordinates cellular responses. The molecular aspects of TLR4 signaling in the context of TJs or the epithelial barrier are not fully known. We describe the current knowledge and possible networking of the TLR4-signaling with cellular and molecular mechanisms of TJs, lung epithelial barrier function, and resistance to treatment strategies.

show abstract

SIRT7 deficiency suppresses inflammation, induces EndoMT, and increases vascular permeability in primary pulmonary endothelial cells

Cited by 23 publications

References 63 publications

Sirtuin 7 Deficiency Reduces Inflammation and Tubular Damage Induced by an Episode of Acute Kidney Injury

Sirtuin 7 Deficiency Reduces Inflammation and Tubular Damage Induced by an Episode of Acute Kidney Injury

SIRT7 in the aging process

Tight Junctions, the Epithelial Barrier, and Toll-like Receptor-4 During Lung Injury

Contact Info

Product

Resources

About