The Role of Autophagy in Inflammatory Bowel Disease

Shao, Bo-Zong; Yao, Yi; Zhai, Junshan; Zhu, Jiang; Li, Jinping; Wu, Kai

doi:10.3389/fphys.2021.621132

Cited by 36 publications

(29 citation statements)

References 148 publications

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“…Data obtained from the present study were in agreement with the accumulated evidence that there is a strong relationship between autophagy and DSS-induced colitis [ 48 ]. Autophagy in the intestinal epithelium represents a key element in the maintenance of intestinal homeostasis, possibly via augmentation of the immunological functions of Paneth cells in the intestine [ 49 ].…”

Section: Discussionsupporting

confidence: 92%

Perindopril/Ambrosin Combination Mitigates Dextran Sulfate Sodium-Induced Colitis in Mice: Crosstalk between Toll-Like Receptor 4, the Pro-Inflammatory Pathways, and SIRT1/PPAR-γ Signaling

et al. 2022

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Colitis is one of the inflammatory states that affect the intestinal wall and may even predispose to malignancy due to chronic irritation. Although the etiology of colitis is not yet fully explored, a combination of genetic and environmental factors is strongly incriminated. Perindopril is an angiotensin-converting enzyme inhibitor that is used for the management of a wide range of cardiovascular diseases. Ambrosin is a sesquiterpene lactone that was proven to have beneficial effects in disorders characterized by inflammatory nature. The objective of this study is to make a comparison between the effects of perindopril or ambrosin on dextran sulfate sodium (DSS)-induced colitis in mice and to explore the effect of their combination. The present findings indicate that each ambrosin or perindopril alone or in combination is able to ameliorate oxidative stress and suppress the proinflammatory pathways in the colonic tissues of DSS-treated mice via mechanisms related to toll-like receptor 4/nuclear factor kappa B signaling and modulation of peroxisome proliferator-activated receptor gamma/sirtuin-1 levels. In addition, each ambrosin or perindopril alone or in combination inhibits apoptosis and augments the mediators of autophagy in DSS-treated mice. These effects are reflected in the amelioration of the histopathological and electron microscopic changes in the colonic tissues. Interestingly, the most remarkable effects are those encountered with the perindopril/ambrosin combination compared to the groups treated with each of these agents alone. In conclusion, the perindopril/ambrosin combination might represent an effective modality for mitigation of the pathogenic events and the clinical sequelae of colitis.

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Section: Discussionsupporting

confidence: 92%

Perindopril/Ambrosin Combination Mitigates Dextran Sulfate Sodium-Induced Colitis in Mice: Crosstalk between Toll-Like Receptor 4, the Pro-Inflammatory Pathways, and SIRT1/PPAR-γ Signaling

et al. 2022

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“…The second principal mechanism to explain the reduction in mitochondrial mass is an increase in autophagy or more specifically mitophagy, a process which removes damaged mitochondria. Indeed, a plethora of proteins associated with autophagy contribute to the pathogenesis of IBD [ 37 – 39 ]. We found normal amounts of the UQCRC2 subunit of complex III in our patient cohort.…”

Section: Discussionmentioning

confidence: 99%

Expression of Oxidative Phosphorylation Complexes and Mitochondrial Mass in Pediatric and Adult Inflammatory Bowel Disease

Schneider

Özsoy

Zimmermann

et al. 2022

Oxidative Medicine and Cellular Longevity

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Introduction. Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a multifactorial intestinal disorder but its precise etiology remains elusive. As the cells of the intestinal mucosa have high energy demands, mitochondria may play a role in IBD pathogenesis. The present study is aimed at evaluating the expression levels of mitochondrial oxidative phosphorylation (OXPHOS) complexes in IBD. Material and Methods. 286 intestinal biopsy samples from the terminal ileum, ascending colon, and rectum from 124 probands (34 CD, 33 UC, and 57 controls) were stained immunohistochemically for all five OXPHOS complexes and the voltage-dependent anion-selective channel 1 protein (VDAC1 or porin). Expression levels were compared in multivariate models including disease stage (CD and UC compared to controls) and age (pediatric/adult). Results. Analysis of the terminal ileum of CD patients revealed a significant reduction of complex II compared to controls, and a trend to lower levels was evident for VDAC1 and the other OXPHOS complexes except complex III. A similar pattern was found in the rectum of UC patients: VDAC1, complex I, complex II, and complex IV were all significantly reduced, and complex III and V showed a trend to lower levels. Reductions were more prominent in older patients compared to pediatric patients and more marked in UC than CD. Conclusion. A reduced mitochondrial mass is present in UC and CD compared to controls. This is potentially a result of alterations of mitochondrial biogenesis or mitophagy. Reductions were more pronounced in older patients compared to pediatric patients, and more prominent in UC than CD. Complex I and II are more severely compromised than the other OXPHOS complexes. This has potential therapeutic implications, since treatments boosting biogenesis or influencing mitophagy could be beneficial for IBD treatment. Additionally, substances specifically stimulating complex I activity should be tested in IBD treatment.

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“…Current studies suggest that the interaction between autophagy, inflammation and gut microbiota affects the disease course of IBD together. [41][42][43] Curcumin is derived from natural products, with high safety, has the capacity for anti-inflammatory, antioxidant, and regulating autophagy and gut microbiota. 44,45 The regulatory relationship among gut microbiota, inflammation and autophagy, as well as their roles in the occurrence and development of IBD, is a new direction to reveal the pathological mechanism of IBD and to search for therapeutic drug targets.…”

Section: Daysmentioning

confidence: 99%

Anti-Inflammatory Effects of Curcumin in the Inflammatory Diseases: Status, Limitations and Countermeasures

Peng¹,

Ao²,

BaoHua³

et al. 2021

DDDT

245

157

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The Role of Autophagy in Inflammatory Bowel Disease

Cited by 36 publications

References 148 publications

Perindopril/Ambrosin Combination Mitigates Dextran Sulfate Sodium-Induced Colitis in Mice: Crosstalk between Toll-Like Receptor 4, the Pro-Inflammatory Pathways, and SIRT1/PPAR-γ Signaling

Perindopril/Ambrosin Combination Mitigates Dextran Sulfate Sodium-Induced Colitis in Mice: Crosstalk between Toll-Like Receptor 4, the Pro-Inflammatory Pathways, and SIRT1/PPAR-γ Signaling

Expression of Oxidative Phosphorylation Complexes and Mitochondrial Mass in Pediatric and Adult Inflammatory Bowel Disease

Anti-Inflammatory Effects of Curcumin in the Inflammatory Diseases: Status, Limitations and Countermeasures

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