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Study · In vitro (cells) · 2025

2 results

Sirt6 deficiency exacerbates angiotensin II-induced lipid nephrotoxicity by affecting PLD6-derived cardiolipin metabolism in podocytes.

Hao Y, Hu J, Zhang Z, Guan Q, Wang J, Tao Y, Cheng J, Fan Y

Cellular signalling10 May 2025Cited by 6 (Europe PMC)

PMID40355014 (opens in a new tab)DOI10.1016/j.cellsig.2025.111858 (opens in a new tab)PepBankPUB-40355014
Publisher pagePubMedAsk about this study
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Summary

Background and aimsPerturbation of cardiolipin (CL) metabolism is associated with lipid nephrotoxicity. Recent findings provide new insights into the roles of CL-modulating proteins as critical determinants of podocyte function in chronic kidney disease (CKD). We previously demonstrated that Sirtuin 6 (Sirt6) is a compelling target inhibiting Angiotensin II (Ang II)-induced lipid dysregulation in podocytes. However, whether Sirt6 regulates podocyte CL metabolism is unknown.MethodsRenal biopsy specimens of patients with hypertensive nephropathy (HN) were used in this study. Podocyte Sirt6-specific knockout mice were generated using the Cre-loxP system. The effect of Sirt6 on mitochondrial CL metabolism, especially the peroxidation and hydrolysis of CL, was investigated in Ang II-infusion mice and Ang II-induced cultured podocytes.ResultsSirt6 and outer mitochondrial membrane protein phospholipase D family member 6 (PLD6) were decreased in the glomeruli of patients with HN. Ang II downregulated Sirt6 and PLD6 expression in podocytes in vitro and in vivo. Podocyte-specific deletion of Sirt6 exacerbated lipid droplets formation, CL accumulation and peroxidation, aggravated Ang II-induced mitochondrial dysfunction and cell apoptosis. Mechanically, Sirt6 maintained podocyte CL homeostasis, at least in part through PLD6 signaling-mediated CL metabolism. In addition, cardiolipin antioxidant Szeto-Schiller Peptide 31 (SS-31) treatment inhibited Ang II-induced lipid accumulation and CL peroxidation in podocytes.ConclusionsOur findings shed light on Sirt6's regulatory mechanisms on podocyte CL metabolism and suggest exploiting the Sirt6-PLD6 axis as a potential therapeutic target for protecting against lipid nephrotoxicity.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

2 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabIn vitro (cells)Mechanism

    In cultured podocytes, SS‑31 treatment inhibited Ang II-induced lipid accumulation.

    In plain wordsIn lab tests on kidney cells, SS‑31 reduced fat build-up caused by angiotensin II.

    Peptide
    Elamipretide (SS-31)
    Outcome
    DecreaseAng II-induced lipid accumulation
    Study

    n: not reported in source

    Ang II-induced cultured podocytes
    Outcome group
    Kidney function · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    cardiolipin antioxidant Szeto-Schiller Peptide 31 (SS-31) treatment inhibited Ang II-induced lipid accumulation and CL peroxidation in podocytes.
    1 context sentence
    Summary · context
    The effect of Sirt6 on mitochondrial CL metabolism, especially the peroxidation and hydrolysis of CL, was investigated in Ang II-infusion mice and Ang II-induced cultured podocytes.
  2. 02LabIn vitro (cells)Mechanism

    In cultured podocytes, SS‑31 treatment inhibited Ang II-induced cardiolipin peroxidation.

    In plain wordsIn lab tests on kidney cells, SS‑31 reduced oxidative damage to a mitochondrial lipid caused by angiotensin II.

    Peptide
    Elamipretide (SS-31)
    Outcome
    DecreaseAng II-induced cardiolipin peroxidation
    Study

    n: not reported in source

    Ang II-induced cultured podocytes
    Outcome group
    Oxidative stress · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    cardiolipin antioxidant Szeto-Schiller Peptide 31 (SS-31) treatment inhibited Ang II-induced lipid accumulation and CL peroxidation in podocytes.
    1 context sentence
    Summary · context
    The effect of Sirt6 on mitochondrial CL metabolism, especially the peroxidation and hydrolysis of CL, was investigated in Ang II-infusion mice and Ang II-induced cultured podocytes.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    10 Oct 2026, 08:19 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 02:47 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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