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Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease.
Tuesday,2023-01-31 14:01 America/Los_Angeles — ecterry
| Title | Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease. |
| Publication Type | Journal Article |
| Year of Publication | 2022 |
| Authors | Liu, J, Nair, V, Zhao, Y-Y, Chang, D-Y, Limonte, C, Bansal, N, Fermin, D, Eichinger, F, Tanner, EC, Bellovich, KA, Steigerwalt, S, Bhat, Z, Hawkins, JJ, Subramanian, L, Rosas, SE, Sedor, JR, Vasquez, MA, Waikar, SS, Bitzer, M, Pennathur, S, Brosius, FC, de Boer, I, Chen, M, Kretzler, M, Ju, W |
| Corporate/Institutional Authors | Kidney Precision Medicine Project and Michigan Translational Core C-PROBE Investigator Group, Kidney Precision Medicine Project and Michigan Translational Core C-PROBE Investigator Group |
| Journal | Diabetes |
| Volume | 71 |
| Issue | 12 |
| Pagination | 2664-2676 |
| Date Published | 2022 Dec 01 |
| ISSN | 1939-327X |
| Keywords | Angiopoietin-1, Angiopoietin-2, Angiopoietins, Biomarkers, Cohort Studies, Diabetes Mellitus, Diabetic Nephropathies, Disease Progression, Endothelial Cells, Humans, Kidney Failure, Chronic, Receptor, TIE-2, Signal Transduction |
| Abstract | <p>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.</p> |
| DOI | 10.2337/db22-0169 |
| Alternate Journal | Diabetes |
| PubMed ID | 36331122 |
| PubMed Central ID | PMC9750948 |
ePub date:
22/12