Roles of kininogen-1, basement membrane specific heparan sulfate proteoglycan core protein, and roundabout homolog 4 as potential urinary protein biomarkers in diabetic nephropathy

• Main Authors: Piyada Na Nakorn, Supitcha Pannengpetch, Patcharee Isarankura-Na-ayudhya, Chadinee Thippakorn, Ratana Lawung, Nuankanya Sathirapongsasuti, Chagriya Kitiyakara, Piyamitr Sritara, Prin Vathesatogkit, Chartchalerm Isarankura-Na-ayudhya
• Other Authors: Faculty of Medicine, Ramathibodi Hospital, Mahidol University
• Format: Article
• Published: 2020
• Subjects: Agricultural and Biological Sciences; Biochemistry, Genetics and Molecular Biology; Pharmacology, Toxicology and Pharmaceutics
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/57638
• Institution: Mahidol University

© 2020, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved. Diabetic nephropathy, a major complication of diabetes mellitus (DM), is increasing worldwide and the large majority of patients have type 2 DM. Microalbuminuria has been used as a diagnostic marker of diabetic nephropathy. But owing to its insufficient sensitivity and specificity, other biomarkers are being sought. In addition, the pathophysiology of diabetic nephropathy is not fully understood and declines in renal function occur even without microalbuminuria. In this study, we investigated urinary proteins from three study groups (controls, and type 2 diabetic subjects with or without microalbuminuria). Non-targeted label-free Nano-LC QTOF analysis was conducted to discover underlying mechanisms and protein networks, and targeted label-free Nano-LC QTOF with SWATH was performed to qualify discovered protein candidates. Twenty-eight proteins were identified as candidates and functionally analyzed via String DB, gene ontology and pathway analysis. Four predictive mechanisms were analyzed: i) response to stimulus, ii) platelet activation, signaling and aggregation, iii) ECM-receptor interaction, and iv) angiogenesis. These mechanisms can provoke kidney dysfunction in type 2 diabetic patients via endothelial cell damage and glomerulus structural alteration. Based on these analyses, three proteins (kininogen-1, basement membrane-specific heparan sulfate proteoglycan core protein, and roundabout homolog 4) were proposed for further study as potential biomarkers. Our findings provide insights that may improve methods for both prevention and diagnosis of diabetic nephropathy.