Diacerein mitigates adenine-induced chronic kidney disease in rats: Focus on TLR4/MYD88/TRAF6/NF-κB pathway

Samaha, Mahmoud M.; Nour, Omnia A.; Sewilam, Haitham M.; El-Kashef, Dalia H.

doi:10.1016/j.lfs.2023.122080

Cited by 3 publications

(1 citation statement)

References 21 publications

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“…TRAF6, a member of this family, plays a role in the pathogenesis of various renal diseases by regulating the activation of NF-κB [ 13–15 ]. In adenine-induced mice, elevated renal levels of TRAF6, NF-κB p65 and p-NF-κB p65 were observed [ 16 ]., TRAF6 silencing can protect against inflammation in LPS-induced HK-2 cells, while TRAF6 overexpression mitigates the inhibition of p-NF-κB p65 and inflammation [ 15 , 17 ]. These findings underscore the importance of the TRAF6-mediated NF-κB pathway in regulating inflammation in renal disease.…”

Section: Introductionmentioning

confidence: 99%

Astragaloside IV relieves passive heymann nephritis and podocyte injury by suppressing the TRAF6/NF-κb axis

Ma,

Hu,

Ruan

et al. 2024

Renal Failure

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The pathogenesis of membranous nephropathy (MN) involves podocyte injury that is attributed to inflammatory responses induced by local immune deposits. Astragaloside IV (AS-IV) is known for its robust anti-inflammatory properties. Here, we investigated the effects of AS-IV on passive Heymann nephritis (PHN) rats and TNF-α-induced podocytes to determine the underlying molecular mechanisms of MN. Serum biochemical parameters, 24-h urine protein excretion and renal histopathology were evaluated in PHN and control rats. The expression of tumor necrosis factor receptor associated factor 6 (TRAF6), the phosphorylation of nuclear factor kappa B (p-NF-κB), the expression of associated proinflammatory cytokines (TNF-α, IL-6 and IL-1β) and the ubiquitination of TRAF6 were measured in PHN rats and TNF-α-induced podocytes. We detected a marked increase in mRNA expression of TNF-α, IL-6 and IL-1β and in the protein abundance of p-NF-κB and TRAF6 within the renal tissues of PHN rats and TNF-α-induced podocytes. Conversely, there was a reduction in the K48-linked ubiquitination of TRAF6. Additionally, AS-IV was effective in ameliorating serum creatinine, proteinuria, and renal histopathology in PHN rats. This effect was concomitant with the suppression of NF-κB pathway activation and decreased expression of TNF-α, IL-6, IL-1β and TRAF6. AS-IV decreased TRAF6 levels by promoting K48-linked ubiquitin conjugation to TRAF6, which triggered ubiquitin-mediated degradation. In summary, AS-IV averted renal impairment in PHN rats and TNF-α-induced podocytes, likely by modulating the inflammatory response through the TRAF6/NF-κB axis. Targeting TRAF6 holds therapeutic promise for managing MN.

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