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Study · Animal study (in vivo) · mouse · 2022

5 results

Targeting the innate repair receptor axis via erythropoietin or pyroglutamate helix B surface peptide attenuates hemolytic-uremic syndrome in mice.

Dennhardt S, Pirschel W, Wissuwa B, Imhof D, Daniel C, Kielstein JT, Hennig-Pauka I, Amann K, Gunzer F, Coldewey SM

Frontiers in immunology23 Sept 2022Cited by 4 (Europe PMC)

PMID36211426 (opens in a new tab)PMCIDPMC9537456 (opens in a new tab)DOI10.3389/fimmu.2022.1010882 (opens in a new tab)PepBankPUB-36211426
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Summary

Hemolytic-uremic syndrome (HUS) can occur as a systemic complication of infections with Shiga toxin (Stx)-producing Escherichia coli and is characterized by microangiopathic hemolytic anemia and acute kidney injury. Hitherto, therapy has been limited to organ-supportive strategies. Erythropoietin (EPO) stimulates erythropoiesis and is approved for the treatment of certain forms of anemia, but not for HUS-associated hemolytic anemia. EPO and its non-hematopoietic analog pyroglutamate helix B surface peptide (pHBSP) have been shown to mediate tissue protection via an innate repair receptor (IRR) that is pharmacologically distinct from the erythropoiesis-mediating receptor (EPO-R). Here, we investigated the changes in endogenous EPO levels in patients with HUS and in piglets and mice subjected to preclinical HUS models. We found that endogenous EPO was elevated in plasma of humans, piglets, and mice with HUS, regardless of species and degree of anemia, suggesting that EPO signaling plays a role in HUS pathology. Therefore, we aimed to examine the therapeutic potential of EPO and pHBSP in mice with Stx-induced HUS. Administration of EPO or pHBSP improved 7-day survival and attenuated renal oxidative stress but did not significantly reduce renal dysfunction and injury in the employed model. pHBSP, but not EPO, attenuated renal nitrosative stress and reduced tubular dedifferentiation. In conclusion, targeting the EPO-R/IRR axis reduced mortality and renal oxidative stress in murine HUS without occurrence of thromboembolic complications or other adverse side effects. We therefore suggest that repurposing EPO for the treatment of patients with hemolytic anemia in HUS should be systematically investigated in future clinical trials.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In mice with Stx-induced HUS, pHBSP improved 7-day survival.

    In plain wordsIn mice with hemolytic-uremic syndrome, pHBSP improved survival over seven days.

    Peptide
    Cibinetide (ARA-290)
    Outcome
    Increase7-day survival
    Study

    mousen: not reported in source

    Mice with Stx-induced hemolytic-uremic syndrome
    Outcome group
    Mortality · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Administration of EPO or pHBSP improved 7-day survival
    1 context sentence
    Summary · context
    Therefore, we aimed to examine the therapeutic potential of EPO and pHBSP in mice with Stx-induced HUS.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In mice with Stx-induced HUS, pHBSP attenuated renal oxidative stress.

    In plain wordsIn mice with hemolytic-uremic syndrome, pHBSP reduced oxidative stress in the kidney.

    Peptide
    Cibinetide (ARA-290)
    Outcome
    DecreaseRenal oxidative stress
    Study

    mousen: not reported in source

    Mice with Stx-induced hemolytic-uremic syndrome
    Outcome group
    Kidney function · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Administration of EPO or pHBSP improved 7-day survival and attenuated renal oxidative stress
    1 context sentence
    Summary · context
    Therefore, we aimed to examine the therapeutic potential of EPO and pHBSP in mice with Stx-induced HUS.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In mice with Stx-induced HUS, pHBSP did not significantly reduce renal dysfunction and injury.

    In plain wordsIn mice with hemolytic-uremic syndrome, pHBSP did not significantly reduce kidney dysfunction or injury.

    Peptide
    Cibinetide (ARA-290)
    Outcome
    No significant changeRenal dysfunction and injury
    Study

    mousen: not reported in source

    Mice with Stx-induced hemolytic-uremic syndrome
    Outcome group
    Kidney function · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    but did not significantly reduce renal dysfunction and injury in the employed model. pHBSP, but not EPO, attenuated renal nitrosative stress and reduced tubular dedifferentiation.
    1 context sentence
    Summary · context
    Therefore, we aimed to examine the therapeutic potential of EPO and pHBSP in mice with Stx-induced HUS.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In mice with Stx-induced HUS, pHBSP, but not EPO, attenuated renal nitrosative stress.

    In plain wordsIn mice with hemolytic-uremic syndrome, pHBSP, but not erythropoietin, reduced nitrosative stress in the kidney.

    Peptide
    Cibinetide (ARA-290)
    Outcome
    DecreaseRenal nitrosative stress
    Study

    mousen: not reported in source

    Mice with Stx-induced hemolytic-uremic syndrome
    Outcome group
    Kidney function · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    pHBSP, but not EPO, attenuated renal nitrosative stress and reduced tubular dedifferentiation.
    1 context sentence
    Summary · context
    Therefore, we aimed to examine the therapeutic potential of EPO and pHBSP in mice with Stx-induced HUS.
  5. 05AnimalAnimal study (in vivo)Efficacy outcome

    In mice with Stx-induced HUS, pHBSP, but not EPO, reduced tubular dedifferentiation.

    In plain wordsIn mice with hemolytic-uremic syndrome, pHBSP, but not erythropoietin, reduced kidney tubule dedifferentiation.

    Peptide
    Cibinetide (ARA-290)
    Outcome
    DecreaseTubular dedifferentiation
    Study

    mousen: not reported in source

    Mice with Stx-induced hemolytic-uremic syndrome
    Outcome group
    Kidney function · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    pHBSP, but not EPO, attenuated renal nitrosative stress and reduced tubular dedifferentiation.
    1 context sentence
    Summary · context
    Therefore, we aimed to examine the therapeutic potential of EPO and pHBSP in mice with Stx-induced HUS.

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

    9 Oct 2026, 19:08 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:13 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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