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Interaction of uromodulin and complement factor H enhances C3b inactivation

Maojing Liu1,2,3,4, Yaqin Wang1,2,3,4, Fengmei Wang1,2,3,4

  • 1Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.

Journal of Cellular and Molecular Medicine
|April 27, 2016
PubMed

Insights

Uromodulin interacts with Complement factor H (CFH) to regulate the complement system. This interaction enhances CFH

Area of Science:

  • Nephrology
  • Immunology
  • Molecular Biology

Background:

  • Uromodulin is implicated in chronic kidney diseases and interacts with immune components.
  • Complement factor H (CFH) regulates the complement alternative pathway and is linked to renal diseases.

Purpose of the Study:

  • To investigate the interaction between uromodulin and CFH in the context of tubulointerstitial injury.
  • To determine if uromodulin regulates complement activation through CFH.

Main Methods:

  • Immunofluorescence to detect co-localization of uromodulin and CFH in renal tubules.
  • Surface plasmon resonance to confirm in vitro binding and determine affinity.
  • Identification of CFH binding sites for uromodulin.

Main Results:

  • Uromodulin and CFH co-localize in renal tubules.
  • Uromodulin binds to CFH with an affinity constant (KD) of 4.07 × 10⁻⁶ M.
  • Binding occurs at specific short consensus repeat (SCR) units on CFH (SCR1-4, SCR7, SCR19-20).
  • The uromodulin-CFH interaction enhances CFH's cofactor activity in cleaving C3b to iC3b.

Conclusions:

  • Uromodulin plays a role in renal tubulointerstitial injury by interacting with and enhancing the function of CFH.
  • This interaction modulates complement activation, suggesting a therapeutic target for kidney diseases.

Keywords:
Tamm-Horsfall proteinchronic kidney diseasecomplement factor Huromodulin

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