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The importance of sialic acid,pH and ion concentration on the interaction of uromodulin and complement factor H |
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| Authors: | Lufeng Bai Qiuyu Xie Min Xia Kunjing Gong Na Wang Yuqing Chen Minghui Zhao |
| Institution: | 1. Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
Peking University Institute of Nephrology, 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 Contribution: Data curation (equal), Investigation (equal), Writing - original draft (equal);2. Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China Peking University Institute of Nephrology, 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 Contribution: Data curation (equal), Investigation (equal), Writing - original draft (equal);3. Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China Peking University Institute of Nephrology, 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 Contribution: Investigation (equal);4. Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China Peking University Institute of Nephrology, 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 Contribution: Methodology (equal);5. Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China;6. Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China Peking University Institute of Nephrology, 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 Contribution: Writing - review & editing (equal) |
| Abstract: | Uromodulin (UMOD) can bind complement factor H (cFH) and inhibit the activation of complement alternative pathway (AP) by enhancing the cofactor activity of cFH on degeneration of C3b. UMOD, an N-glycans-rich glycoprotein, is expressed in thick ascending limb of Henle's loop where the epithelia need to adapt to gradient change of pH and ion concentration. ELISA-based cofactor activity of cFH and erythrocytes haemolytic assay was used to measure the impact of native and de-glycosylated UMOD on the functions of cFH. The binding assay was performed under different pH and ion concentrations, using ELISA. The levels of sialic acid on UMOD, from healthy controls and patients with chronic kidney disease (CKD), were also detected by lectin-ELISA. It was shown that removal of glycans decreased the binding between UMOD and cFH and abolished the ability of enhancing C3b degradation. In acidic condition, the binding became stronger, but it reduced as sodium concentration increased. A significant decrease of α-2,3 sialic acids on UMOD was observed in CKD patients compared with that of healthy individuals. The sialic acids on UMOD, local pH and sodium concentration could impact the binding capacity between UMOD and cFH and thus regulate the activation of complement AP. |
| Keywords: | complement factor H pH sialic acid sodium Uromodulin |