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

Authors

  • Piyada Na Nakorn Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand
  • Supitcha Pannengpetch Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, Nakornpathom, Thailand
  • Patcharee Isarankura-Na-Ayudhya Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumthani, Thailand
  • Chadinee Thippakorn Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, Nakornpathom, Thailand
  • Ratana Lawung Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand
  • Nuankanya Sathirapongsasuti Section for Translational Medicine, Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  • Chagriya Kitiyakara Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  • Piyamitr Sritara Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  • Prin Vathesatogkit Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  • Chartchalerm Isarankura-Na-Ayudhya Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand. Phone: +662-441-4370-9 ext. 2845; Fax: +66 2 441 4380, E-mail: chartchalerm.isa@mahidol.ac.th

DOI:

https://doi.org/10.17179/excli2020-2359

Keywords:

diabetic nephropathy, urine, quantitative proteomics

Abstract

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.

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Published

2020-06-24

How to Cite

Na Nakorn, P., Pannengpetch, S., Isarankura-Na-Ayudhya, P., Thippakorn, C., Lawung, R., Sathirapongsasuti, N., … Isarankura-Na-Ayudhya, C. (2020). Roles of kininogen-1, basement membrane specific heparan sulfate proteoglycan core protein, and roundabout homolog 4 as potential urinary protein biomarkers in diabetic nephropathy. EXCLI Journal, 19, 872–891. https://doi.org/10.17179/excli2020-2359

Issue

Vol. 19 (2020)

Section

Original articles

License

Copyright (c) 2020 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

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