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Klotho alleviates indoxyl sulfate-induced heart failure and kidney damage by promoting M2 macrophage polarization

Jing Lv1, Jin Chen1, Minjia Wang2

  • 1Department of General Practice, Zhejiang Hospital, Hangzhou 310013, Zhejiang, P.R. China.

Aging
|May 29, 2020
PubMed

Insights

Klotho protein can protect against kidney and heart damage caused by indoxyl sulfate (IS), a toxin linked to chronic kidney disease. It works by reducing inflammation and promoting beneficial macrophage changes.

Area of Science:

  • Nephrology
  • Cardiology
  • Immunology

Background:

  • Indoxyl sulfate (IS) is a uremic toxin accumulating in chronic kidney disease (CKD) and acute kidney injury (AKI), causing organ damage.
  • Klotho is an anti-aging protein with known reno- and cardio-protective properties.

Purpose of the Study:

  • To investigate Klotho's potential to mitigate IS-induced heart failure and kidney damage.
  • To explore Klotho's role in regulating macrophage function during IS exposure.

Main Methods:

  • THP-1-derived macrophages were treated with IS to assess inflammatory responses and Klotho expression.
  • Macrophage polarization (M1/M2) and NF-kB signaling pathways were analyzed.
  • Effects of Klotho overexpression on IS-induced cardiac hypertrophy and renal fibrosis in mice were evaluated.

Main Results:

  • IS exposure induced pro-inflammatory cytokines (TNFα, IL-6, IL-1β) and M1 macrophage polarization.
  • IS downregulated Klotho expression in macrophages.
  • Klotho overexpression suppressed IS-induced inflammation, promoted M2 polarization, and alleviated cardiac and renal damage in mice.
  • Klotho overexpression reduced IS-induced NF-kB p65 phosphorylation.

Conclusions:

  • Klotho alleviates IS-induced kidney and cardiac injury.
  • Klotho exerts protective effects by inhibiting NF-kB signaling and promoting M2 macrophage polarization.
Keywords:
Klothocardiovascular diseasechronic kidney diseaseindoxyl sulfatemacrophage polarization

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