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

dc.contributor.authorPiyada Na Nakornen_US
dc.contributor.authorSupitcha Pannengpetchen_US
dc.contributor.authorPatcharee Isarankura-Na-ayudhyaen_US
dc.contributor.authorChadinee Thippakornen_US
dc.contributor.authorRatana Lawungen_US
dc.contributor.authorNuankanya Sathirapongsasutien_US
dc.contributor.authorChagriya Kitiyakaraen_US
dc.contributor.authorPiyamitr Sritaraen_US
dc.contributor.authorPrin Vathesatogkiten_US
dc.contributor.authorChartchalerm Isarankura-Na-ayudhyaen_US
dc.contributor.otherFaculty of Medicine, Ramathibodi Hospital, Mahidol Universityen_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherThammasat Universityen_US
dc.description.abstract© 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.en_US
dc.identifier.citationEXCLI Journal. Vol.19, (2020), 872-891en_US
dc.rightsMahidol Universityen_US
dc.subjectAgricultural and Biological Sciencesen_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.subjectPharmacology, Toxicology and Pharmaceuticsen_US
dc.titleRoles of kininogen-1, basement membrane specific heparan sulfate proteoglycan core protein, and roundabout homolog 4 as potential urinary protein biomarkers in diabetic nephropathyen_US