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.

Authors:

J Cell Biochem 2019 Apr 19. Epub 2019 Apr 19.

Internal Medicine Department, Faculty of Medicine, Tanta University, Tanta, Egypt.

Background: Chronic kidney disease (CKD) signifies a frequently life-threatening condition influencing kidney structure and function. Despite its irrefutable importance, its exact pathogenesis is not completely clarified. However, CKD is known to be associated with accumulated uremic toxins/metabolites, interstitial fibrosis, and systemic inflammation. So we aimed to investigate the role of microbiota-dependent metabolite trimethylamine N-oxide (TMAO), transforming growth factor β (TGFβ)/SMAD signaling, and inflammasome activation in CKD pathogenesis through its different stages.

Subjects And Methods: Eighty patients with CKD of stages 2 to 4 in addition 15 healthy control subjects were enrolled. SMAD3 and nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3) messenger RNA (mRNA) expressions from whole blood were assessed by quantitative real-time polymerase chain reaction (RT-PCR). Serum TGF-β1 and interleukin-1β (IL-1β) levels were estimated by the enzyme-linked immunosorbent assay. Plasma and urinary TMAO levels were measured. Oxidative stress markers were also assessed.

Results: SMAD3 and NLRP3 mRNA expressions were significantly upregulated in patients with CKD. Likewise, serum TGF-β1 and IL-1β levels were significantly elevated in patients with CKD, with increase in plasma and urinary TMAO levels and altered redox status throughout different CKD stages.

Conclusion: The study documented that TMAO could be used as a reliable biomarker to evaluate CKD progression; being linked to TGF-β/SMAD signaling, NLRP3 inflammasome activation as well as being a noninvasive applicable technique.

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https://onlinelibrary.wiley.com/doi/abs/10.1002/jcb.28707
Publisher Site
http://dx.doi.org/10.1002/jcb.28707DOI Listing

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April 2019
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