The interplay between microbiota‐dependent metabolite trimethylamine <i>N</i>‐oxide, Transforming growth factor <i>β</i>/SMAD signaling and inflammasome activation in chronic kidney disease patients: A new mechanistic perspective

El-Deeb, Omnia Safwat; Atef, Marwa Mohamed; Hafez, Yasser Mostafa

doi:10.1002/jcb.28707

Cited by 35 publications

(27 citation statements)

References 47 publications

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“…When mice were fed a diet supplemented with TMAO or high fat, enhanced SMAD3 phosphorylation, tubulointerstitial fibrosis, and collagen deposition were observed. These results were verified in a CKD cohort (Tang et al, 2015;Sun et al, 2017;El-Deeb et al, 2019).…”

Section: Intestinal Microbiota and Nephritic Fibrosissupporting

confidence: 60%

Intestinal Fibrosis and Gut Microbiota: Clues From Other Organs

Zhan

Liu

et al. 2021

Front. Microbiol.

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Fibrosis is a complex and difficult to elucidate pathological process with no available therapies. Growing evidence implicates intestinal microbiota in the occurrence and development of fibrosis, and the potential mechanisms involved in different organs have been explored in several studies. In this review, we summarize the causative and preventive effects of gut microbiota on intestinal fibrosis, as well as the relationships between gut microbiota and fibrosis in other organs. Interestingly, several colonized microbes are associated with fibrosis via their structural components and metabolic products. They may also play essential roles in regulating inflammation and fibroblast activation or differentiation, which modulates extracellular matrix formation. While the relationships between intestinal fibrosis and gut microbiota remain unclear, lessons can be drawn from the effects of gut microbiota on hepatic, cardiac, nephritic, and pulmonary fibrosis. Various intestinal microbes alterations have been detected in different fibrotic organs; however, the results were heterogeneous. Mechanisms by which the intestinal microbiota regulate fibrotic processes in other organs, such as novel metabolic products or specific microbes, are also discussed. The specific microbiota associated with fibrosis in other organs could instruct future studies aiming to discover prospective mechanisms regulating intestinal fibrosis.

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Section: Intestinal Microbiota and Nephritic Fibrosissupporting

confidence: 60%

Intestinal Fibrosis and Gut Microbiota: Clues From Other Organs

Zhan

Liu

et al. 2021

Front. Microbiol.

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“…Recent studies have confirmed that TGF-beta stimulation was found to induce NLRP3 abundance in a Smad3-dependent manner, and NLRP3 can also promote the progression of renal tubular EMT via the enhancement of TGF-beta signaling and the activation of R-Smad (Lorenz et al, 2014;El-Deeb et al, 2019). In the present study, compared to Ang II stimulation (Figures 3A-C), the NRK-52E cells are more sensitive to TGF-beta, in which the fibrotic marker alpha-SMA and CollagenI were significantly upregulated in 72 h (Figures 3D-I).…”

Section: Discussionmentioning

confidence: 93%

Contribution of TGF-Beta-Mediated NLRP3-HMGB1 Activation to Tubulointerstitial Fibrosis in Rat With Angiotensin II-Induced Chronic Kidney Disease

Zhang

Fan

Cai

et al. 2020

Front. Cell Dev. Biol.

178

130

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Fibrosis is a common phenotype that often leads to the progression of blood pressure-induced chronic kidney disease (CKD). TGF-beta plays an important role in promoting pathogenesis, and NLRP3 is a critical mediator in the progression of blood pressure-induced CKD. However, the pathophysiological roles of the TGF-betamediated NLRP3 pathway in modulating fibrosis in blood pressure-induced CKD have not been elucidated. The present study aims to investigate the contribution of TGFbeta-mediated NLRP3 inflammasome to renal fibrosis in rats with high blood pressure. By treating rats with angiotensin II (Ang II) for 14 days, we observed the development of fibrosis, characterized by epithelial-mesenchymal transition (EMT) markers [alphasmooth muscle actin (alpha-SMA), MMP-2, and MMP-9]. Immunohistochemical analysis further revealed that TGF-beta and NLRP3 inflammasome activation [high-mobility group box 1 (HMGB1), IL-1beta, and NLRP3] were significantly upregulated in the kidney of rats with Ang II-induced hypertension. Interestingly, we observed that Ang II could not increase the production of NLRP3 proteins, but TGF-beta could induce NLRP3 protein expression in cultured NRK-52E cells. Furthermore, we speculated that TGF-beta played a pathogenic role in Ang II-induced CKD because TGF-beta induced the activation of NLRP3 inflammasomes and Gasdermin D cleavage expression. We also proved that the pharmacological inhibition of NLRP3 by ISO caused a decrease in TGF-beta-induced NLRP3 inflammasome activation and the expression of EMT markers (alpha-SMA and CollagenI) and Gasdermin D cleavage. Collectively, these results suggest that TGF-beta-mediated NLRP3 inflammasome activation may cause the release of HMGB1 and an increase in Gasdermin D cleavage in NRK-52E, thereby contributing to renal fibrosis in Ang II-induced CKD. These findings provide novel insights into the pathogenic role of NLRP3 in CKD associated with high blood pressure.

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“…Similar to other human microbial communities, the urinary microbiota could play a role in modulating the immune response (Jones-Freeman et al, 2021). In fact, it has been shown that some microbial metabolites may be involved in the regulation of the immune response and inflammation during urinary diseases (El-Deeb et al, 2019).…”

Section: Urinary Microbiome or Urobiomementioning

confidence: 99%

Urinary Microbiome: Yin and Yang of the Urinary Tract

Pérez-Carrasco

Soriano‐Lerma

Soriano

et al. 2021

Front. Cell. Infect. Microbiol.

137

119

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The application of next generation sequencing techniques has allowed the characterization of the urinary tract microbiome and has led to the rejection of the pre-established concept of sterility in the urinary bladder. Not only have microbial communities in the urinary tract been implicated in the maintenance of health but alterations in their composition have also been associated with different urinary pathologies, such as urinary tract infections (UTI). Therefore, the study of the urinary microbiome in healthy individuals, as well as its involvement in disease through the proliferation of opportunistic pathogens, could open a potential field of study, leading to new insights into prevention, diagnosis and treatment strategies for urinary pathologies. In this review we present an overview of the current state of knowledge about the urinary microbiome in health and disease, as well as its involvement in the development of new therapeutic strategies.

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The interplay between microbiota‐dependent metabolite trimethylamine N‐oxide, Transforming growth factor β/SMAD signaling and inflammasome activation in chronic kidney disease patients: A new mechanistic perspective

Cited by 35 publications

References 47 publications

Intestinal Fibrosis and Gut Microbiota: Clues From Other Organs

Intestinal Fibrosis and Gut Microbiota: Clues From Other Organs

Contribution of TGF-Beta-Mediated NLRP3-HMGB1 Activation to Tubulointerstitial Fibrosis in Rat With Angiotensin II-Induced Chronic Kidney Disease

Urinary Microbiome: Yin and Yang of the Urinary Tract

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