Interaction of uromodulin and complement factor H enhances C3b inactivation
Open Access
- 26 April 2016
- journal article
- Published by Wiley in Journal of Cellular and Molecular Medicine
- Vol. 20 (10), 1821-1828
- https://doi.org/10.1111/jcmm.12872
Abstract
Recent studies suggest that uromodulin plays an important role in chronic kidney diseases. It can interact with several complement components, various cytokines and immune system cells. Complement factor H (CFH), as a regulator of the complement alternative pathway, is also associated with various renal diseases. Thus, we have been suggested that uromodulin regulates complement activation by interacting with CFH during tubulointerstitial injury. We detected co‐localization of uromodulin and CFH in the renal tubules by using immunofluorescence. Next, we confirmed the binding of uromodulin with CFH in vitro and found that the affinity constant (KD) of uromodulin binding to CFH was 4.07 × 10−6M based on surface plasmon resonance results. The binding sites on CFH were defined as the short consensus repeat (SCR) units SCR1–4, SCR7 and SCR19–20. The uromodulin‐CFH interaction enhanced the cofactor activity of CFH for factor I‐mediated cleavage of C3b to iC3b. These results indicate that uromodulin plays a role via binding and enhancing the function of CFH.Keywords
Funding Information
- National Natural Science Foundation of China (81270820)
This publication has 37 references indexed in Scilit:
- Urinary Uromodulin Excretion Predicts Progression of Chronic Kidney Disease Resulting from IgA NephropathyPLOS ONE, 2013
- Common genetic variants of the human uromodulin gene regulate transcription and predict plasma uric acid levelsKidney International, 2013
- Binding of factor H to tubular epithelial cells limits interstitial complement activation in ischemic injuryKidney International, 2011
- Tamm-Horsfall protein-deficient thick ascending limbs promote injury to neighboring S3 segments in an MIP-2-dependent mechanismAmerican Journal of Physiology-Renal Physiology, 2011
- Complement control protein factor H: The good, the bad, and the inadequateMolecular Immunology, 2010
- Association of Variants at UMOD with Chronic Kidney Disease and Kidney Stones—Role of Age and Comorbid DiseasesPLoS Genetics, 2010
- Multiple loci associated with indices of renal function and chronic kidney diseaseNature Genetics, 2009
- Binding of Tamm‐Horsfall protein to complement 1q measured by ELISA and resonant mirror biosensor techniques under various ionic‐strength conditionsImmunology & Cell Biology, 2000
- Differential expression of complement components in human fetal and adult kidneysKidney International, 1996
- Regulation of C3 and factor H synthesis of human glomerular mesangial cells by IL-1 and interferon-gammaClinical and Experimental Immunology, 1994