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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2022
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.
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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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