Sirtuins as endogenous regulators of lung fibrosis: A current perspective

Mazumder, Somnath; Barman, Mukta; Bandyopadhyay, Uday

doi:10.1016/j.lfs.2020.118201

Cited by 46 publications

(42 citation statements)

References 178 publications

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“…9 It has been estimated that fibrosis can account for up to 45% of global deaths in western countries, thus representing a major concern to public health. 10,11 In this context, the scientific community devoted a large effort to identify the underlying molecular mechanisms and potential therapeutic targets. 11 Data collected so far suggest that appropriate therapies can effectively stop or even reverse fibrosis.…”

Section: Fibrotic Diseasesmentioning

confidence: 99%

“…[73][74][75][76][77][78][79][80][81][82] Interestingly, sirtuins can prevent the fibrogenic response through the modulation of many fibrogenic processes, such as FMT, EMT, EndMT and intracellular fibrogenic signallings, such as TGF-β, Wnt and mTOR pathways (Figure 1; Table 1). 10 Moreover, sirtuins regulate other signalling determinants of fibrosis, such as ROS levels, autophagy, insulin-like growth factor (IGF)/protein kinase b alpha (AKT) and nuclear factor kappa b (NF-κB) (Figure 1; Table 1). 10…”

Section: Sirtuins and Pro-fibrotic Signalling Pathwaysmentioning

confidence: 99%

“…10 Moreover, sirtuins regulate other signalling determinants of fibrosis, such as ROS levels, autophagy, insulin-like growth factor (IGF)/protein kinase b alpha (AKT) and nuclear factor kappa b (NF-κB) (Figure 1; Table 1). 10…”

Section: Sirtuins and Pro-fibrotic Signalling Pathwaysmentioning

confidence: 99%

“…9 Noteworthy, sirtuins have been demonstrated to interplay with key proteins involved in both the canonical and non-canonical TGF-β signalling pathways. 10,26,[90][91][92] In particular, Sirt1, mainly through its deacetylating activity on Smad proteins, inhibits profibrotic processes. 2,26,31,34 As for Sirt2, it favours the development of fibrosis by activating the ERK pathways.…”

Section: Tgf-β Pathwaymentioning

confidence: 99%

“…37 Also, it has been hypothesised that Sirt2 could exert a pro-fibrotic activity in lung fibrosis. 10…”

Section: Sirt2 and Fibrosismentioning

confidence: 99%

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Fibrosis: Sirtuins at the checkpoints of myofibroblast differentiation and profibrotic activity

Zullo

Mancini

Schleip

et al. 2021

Wound Repair Regeneration

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Fibrotic diseases are still a serious concern for public health, due to their high prevalence, complex etiology and lack of successful treatments. Fibrosis consists of excessive accumulation of extracellular matrix components. As a result, the structure and function of tissues are impaired, thus potentially leading to organ failure and death in several chronic diseases. Myofibroblasts represent the principal cellular mediators of fibrosis, due to their extracellular matrix producing activity, and originate from different types of precursor cells, such as mesenchymal cells, epithelial cells and fibroblasts. Profibrotic activation of myofibroblasts can be triggered by a variety of mechanisms, including the transforming growth factor-β signalling pathway, which is a major factor driving fibrosis. Interestingly, preclinical and clinical studies showed that fibrotic degeneration can stop and even reverse by using specific antifibrotic treatments. Increasing scientific evidence is being accumulated about the role of sirtuins in modulating the molecular pathways responsible for the onset and development of fibrotic diseases. Sirtuins are NAD +dependent protein deacetylases that play a crucial role in several molecular pathways within the cells, many of which at the crossroad between health and disease. In this context, we will report the current knowledge supporting the role of sirtuins in the balance between healthy and diseased myofibroblast activity. In particular, we will address the signalling pathways and the molecular targets that trigger the differentiation and profibrotic activation of myofibroblasts and can be modulated by sirtuins.

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Section: Fibrotic Diseasesmentioning

confidence: 99%

Section: Sirtuins and Pro-fibrotic Signalling Pathwaysmentioning

confidence: 99%

Section: Sirtuins and Pro-fibrotic Signalling Pathwaysmentioning

confidence: 99%

Section: Tgf-β Pathwaymentioning

confidence: 99%

“…37 Also, it has been hypothesised that Sirt2 could exert a pro-fibrotic activity in lung fibrosis. 10…”

Section: Sirt2 and Fibrosismentioning

confidence: 99%

See 3 more Smart Citations

Fibrosis: Sirtuins at the checkpoints of myofibroblast differentiation and profibrotic activity

Zullo

Mancini

Schleip

et al. 2021

Wound Repair Regeneration

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Idiopathic Pulmonary Fibrosis Caused by Damaged Mitochondria and Imbalanced Protein Homeostasis in Alveolar Epithelial Type II Cell

Dong,

Wang,

Wang

et al. 2024

Advanced Biology

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Alveolar epithelial Type II (ATII) cells are closely associated with early events of Idiopathic pulmonary fibrosis (IPF). Proteostasis dysfunction, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction are known causes of decreased proliferation of alveolar epithelial cells and the secretion of pro‐fibrotic mediators. Here, a large body of evidence is systematized and a cascade relationship between protein homeostasis, endoplasmic reticulum stress, mitochondrial dysfunction, and fibrotropic cytokines is proposed, providing a theoretical basis for ATII cells dysfunction as a possible pathophysiological initiating event for idiopathic pulmonary fibrosis.

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AGK2, a SIRT2 inhibitor, ameliorates D‐galactose‐induced liver fibrosis by inhibiting fibrogenic factors

Bahar,

Keskin‐Aktan,

Akarca‐Dizakar

et al. 2024

J Biochem & Molecular Tox

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In our study, we aimed to investigate the effect of SIRT2 inhibition on function, fibrosis and inflammation in liver fibrosis induced by D‐Galactose (D‐Gal) administration. A total of 32 3‐month‐old Sprague Dawley rats were used in the study. Rats were divided into 4 groups as Control, d‐Gal, Solvent+d‐Gal, d‐Gal+AGK2+Solvent. d‐Gal (150 mg/kg/day), AGK‐2 (10 µM/bw) as a specific SIRT2 inhibitor, 4%DMSO + PBS as a solvent was applied to the experimental groups and physiological saline was applied to the control group for 10 weeks. All applications were performed subcutaneously. Histological fibrotic changes were studied in the liver tissues by Masson's trichrome staining, hematoxylin and eosin staining and immunohistochemistry and the levels of selected factors were determined by quantitative reverse transcription‐polymerase chain reaction, western blot analysis, and immunohistochemical analysis. Biochemical parameters and Paraoxonase levels were determined in the plasma. d‐Galactose administration increased AST, AST‐ALT Ratio, APRI, SIRT2 protein expression, IL1β, TGF β, β‐catenin, Type I collagen, Type III collagen and α‐SMA, collagen fiber density and histopathological score. ALT and lipid panels were not changed and paraxonase plasma level was shown to decrease. These effects were largely blocked by the SIRT2 inhibitor AGK2. These findings suggest that SIRT2 inhibition attenuates d‐Gal‐induced liver injury and that this protection may be due to its antifibrotic and anti‐inflammatory activities.

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Sirtuins as endogenous regulators of lung fibrosis: A current perspective

Cited by 46 publications

References 178 publications

Fibrosis: Sirtuins at the checkpoints of myofibroblast differentiation and profibrotic activity

Fibrosis: Sirtuins at the checkpoints of myofibroblast differentiation and profibrotic activity

Idiopathic Pulmonary Fibrosis Caused by Damaged Mitochondria and Imbalanced Protein Homeostasis in Alveolar Epithelial Type II Cell

AGK2, a SIRT2 inhibitor, ameliorates D‐galactose‐induced liver fibrosis by inhibiting fibrogenic factors

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