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Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease
Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD). Prognostic biomarkers reflective of underlying molecular mechanisms are critically needed for effective management of DKD. A three-marker panel was derived from a proteomics analysis of plasma samples by an unbias...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9750948/ https://www.ncbi.nlm.nih.gov/pubmed/36331122 http://dx.doi.org/10.2337/db22-0169 |
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author | Liu, Jiahao Nair, Viji Zhao, Yi-yang Chang, Dong-yuan Limonte, Christine Bansal, Nisha Fermin, Damian Eichinger, Felix Tanner, Emily C. Bellovich, Keith A. Steigerwalt, Susan Bhat, Zeenat Hawkins, Jennifer J. Subramanian, Lalita Rosas, Sylvia E. Sedor, John R. Vasquez, Miguel A. Waikar, Sushrut S. Bitzer, Markus Pennathur, Subramaniam Brosius, Frank C. De Boer, Ian Chen, Min Kretzler, Matthias Ju, Wenjun |
author_facet | Liu, Jiahao Nair, Viji Zhao, Yi-yang Chang, Dong-yuan Limonte, Christine Bansal, Nisha Fermin, Damian Eichinger, Felix Tanner, Emily C. Bellovich, Keith A. Steigerwalt, Susan Bhat, Zeenat Hawkins, Jennifer J. Subramanian, Lalita Rosas, Sylvia E. Sedor, John R. Vasquez, Miguel A. Waikar, Sushrut S. Bitzer, Markus Pennathur, Subramaniam Brosius, Frank C. De Boer, Ian Chen, Min Kretzler, Matthias Ju, Wenjun |
author_sort | Liu, Jiahao |
collection | PubMed |
description | Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD). Prognostic biomarkers reflective of underlying molecular mechanisms are critically needed for effective management of DKD. A three-marker panel was derived from a proteomics analysis of plasma samples by an unbiased machine learning approach from participants (N = 58) in the Clinical Phenotyping and Resource Biobank study. In combination with standard clinical parameters, this panel improved prediction of the composite outcome of ESKD or a 40% decline in glomerular filtration rate. The panel was validated in an independent group (N = 68), who also had kidney transcriptomic profiles. One marker, plasma angiopoietin 2 (ANGPT2), was significantly associated with outcomes in cohorts from the Cardiovascular Health Study (N = 3,183) and the Chinese Cohort Study of Chronic Kidney Disease (N = 210). Glomerular transcriptional angiopoietin/Tie (ANG-TIE) pathway scores, derived from the expression of 154 ANG-TIE signaling mediators, correlated positively with plasma ANGPT2 levels and kidney outcomes. Higher receptor expression in glomeruli and higher ANG-TIE pathway scores in endothelial cells corroborated potential functional effects in the kidney from elevated plasma ANGPT2 levels. Our work suggests that ANGPT2 is a promising prognostic endothelial biomarker with likely functional impact on glomerular pathogenesis in DKD. |
format | Online Article Text |
id | pubmed-9750948 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-97509482023-01-21 Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease Liu, Jiahao Nair, Viji Zhao, Yi-yang Chang, Dong-yuan Limonte, Christine Bansal, Nisha Fermin, Damian Eichinger, Felix Tanner, Emily C. Bellovich, Keith A. Steigerwalt, Susan Bhat, Zeenat Hawkins, Jennifer J. Subramanian, Lalita Rosas, Sylvia E. Sedor, John R. Vasquez, Miguel A. Waikar, Sushrut S. Bitzer, Markus Pennathur, Subramaniam Brosius, Frank C. De Boer, Ian Chen, Min Kretzler, Matthias Ju, Wenjun Diabetes Pathophysiology Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD). Prognostic biomarkers reflective of underlying molecular mechanisms are critically needed for effective management of DKD. A three-marker panel was derived from a proteomics analysis of plasma samples by an unbiased machine learning approach from participants (N = 58) in the Clinical Phenotyping and Resource Biobank study. In combination with standard clinical parameters, this panel improved prediction of the composite outcome of ESKD or a 40% decline in glomerular filtration rate. The panel was validated in an independent group (N = 68), who also had kidney transcriptomic profiles. One marker, plasma angiopoietin 2 (ANGPT2), was significantly associated with outcomes in cohorts from the Cardiovascular Health Study (N = 3,183) and the Chinese Cohort Study of Chronic Kidney Disease (N = 210). Glomerular transcriptional angiopoietin/Tie (ANG-TIE) pathway scores, derived from the expression of 154 ANG-TIE signaling mediators, correlated positively with plasma ANGPT2 levels and kidney outcomes. Higher receptor expression in glomeruli and higher ANG-TIE pathway scores in endothelial cells corroborated potential functional effects in the kidney from elevated plasma ANGPT2 levels. Our work suggests that ANGPT2 is a promising prognostic endothelial biomarker with likely functional impact on glomerular pathogenesis in DKD. American Diabetes Association 2022-12 2022-11-04 /pmc/articles/PMC9750948/ /pubmed/36331122 http://dx.doi.org/10.2337/db22-0169 Text en © 2022 by the American Diabetes Association https://www.diabetesjournals.org/journals/pages/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/journals/pages/license. |
spellingShingle | Pathophysiology Liu, Jiahao Nair, Viji Zhao, Yi-yang Chang, Dong-yuan Limonte, Christine Bansal, Nisha Fermin, Damian Eichinger, Felix Tanner, Emily C. Bellovich, Keith A. Steigerwalt, Susan Bhat, Zeenat Hawkins, Jennifer J. Subramanian, Lalita Rosas, Sylvia E. Sedor, John R. Vasquez, Miguel A. Waikar, Sushrut S. Bitzer, Markus Pennathur, Subramaniam Brosius, Frank C. De Boer, Ian Chen, Min Kretzler, Matthias Ju, Wenjun Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease |
title | Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease |
title_full | Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease |
title_fullStr | Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease |
title_full_unstemmed | Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease |
title_short | Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease |
title_sort | multi-scalar data integration links glomerular angiopoietin-tie signaling pathway activation with progression of diabetic kidney disease |
topic | Pathophysiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9750948/ https://www.ncbi.nlm.nih.gov/pubmed/36331122 http://dx.doi.org/10.2337/db22-0169 |
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