Interaction of uromodulin and complement factor H enhances C3b inactivation.
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(-6) M 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.
Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.|Institute of Nephrology, Peking University, Beijing, China.|Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.|Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, China.
Maojing
M
Liu
Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.|Institute of Nephrology, Peking University, Beijing, China.|Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.|Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, China.
Yaqin
Y
Wang
Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.|Institute of Nephrology, Peking University, Beijing, China.|Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.|Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, China.
Fengmei
F
Wang
Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.|Institute of Nephrology, Peking University, Beijing, China.|Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.|Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, China.
Min
M
Xia
Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.|Institute of Nephrology, Peking University, Beijing, China.|Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.|Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, China.
Ying
Y
Liu
Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China. cyq@bjmu.edu.cn.|Institute of Nephrology, Peking University, Beijing, China. cyq@bjmu.edu.cn.|Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China. cyq@bjmu.edu.cn.|Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, China. cyq@bjmu.edu.cn.
Yuqing
Y
Chen
Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.|Institute of Nephrology, Peking University, Beijing, China.|Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.|Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, China.|Peking-Tsinghua Center for Life Sciences, Beijing, China.
Ming-Hui
MH
Zhao
D003179:Complement C3b / Q000378:metabolism*; D017242:Complement Factor H / Q000378:metabolism*; D005260:Female; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D011485:Protein Binding; D020349:Surface Plasmon Resonance; D058949:Uromodulin / Q000378:metabolism*
D058949:Uromodulin; D003179:Complement C3b; D017242:Complement Factor H
Tamm-Horsfall protein; chronic kidney disease; complement factor H; uromodulin