Circulating testican-2 is a podocyte-derived marker of kidney health
(2020) In Proceedings of the National Academy of Sciences of the United States of America 117(40). p.25026-25035- Abstract
In addition to their fundamental role in clearance, the kidneys release select molecules into the circulation, but whether any of these anabolic functions provides insight on kidney health is unknown. Using aptamer-based proteomics, we characterized arterial (A)-to-renal venous (V) gradients for >1,300 proteins in 22 individuals who underwent invasive sampling. Although most of the proteins that changed significantly decreased from A to V, consistent with renal clearance, several were found to increase, the most significant of which was testican-2. To assess the clinical implications of these physiologic findings, we examined proteomic data in the Jackson Heart Study (JHS), an African-American cohort (n = 1,928), with replication in... (More)
In addition to their fundamental role in clearance, the kidneys release select molecules into the circulation, but whether any of these anabolic functions provides insight on kidney health is unknown. Using aptamer-based proteomics, we characterized arterial (A)-to-renal venous (V) gradients for >1,300 proteins in 22 individuals who underwent invasive sampling. Although most of the proteins that changed significantly decreased from A to V, consistent with renal clearance, several were found to increase, the most significant of which was testican-2. To assess the clinical implications of these physiologic findings, we examined proteomic data in the Jackson Heart Study (JHS), an African-American cohort (n = 1,928), with replication in the Framingham Heart Study (FHS), a White cohort (n = 1,621). In both populations, testican-2 had a strong, positive correlation with estimated glomerular filtration rate (eGFR). In addition, higher baseline testican-2 levels were associated with a lower rate of eGFR decline in models adjusted for age, gender, hypertension, type 2 diabetes, body mass index, baseline eGFR, and albuminuria. Glomerular expression of testican-2 in human kidneys was demonstrated by immunohistochemistry, immunofluorescence, and electron microscopy, while single-cell RNA sequencing of human kidneys showed expression of the cognate gene, SPOCK2, exclusively in podocytes. In vitro, testican-2 increased glomerular endothelial tube formation and motility, raising the possibility that its secretion has a functional role within the glomerulus. Taken together, our findings identify testican-2 as a podocyte-derived biomarker of kidney health and prognosis.
(Less)
- author
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- chronic kidney disease, proteomics, testican-2
- in
- Proceedings of the National Academy of Sciences of the United States of America
- volume
- 117
- issue
- 40
- pages
- 10 pages
- publisher
- National Academy of Sciences
- external identifiers
-
- pmid:32958645
- scopus:85092680817
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.2009606117
- language
- English
- LU publication?
- yes
- id
- 93f3ae6f-1176-43dd-9e46-3373b4250428
- date added to LUP
- 2020-11-09 07:35:17
- date last changed
- 2024-04-03 16:23:38
@article{93f3ae6f-1176-43dd-9e46-3373b4250428,
abstract = {{<p>In addition to their fundamental role in clearance, the kidneys release select molecules into the circulation, but whether any of these anabolic functions provides insight on kidney health is unknown. Using aptamer-based proteomics, we characterized arterial (A)-to-renal venous (V) gradients for >1,300 proteins in 22 individuals who underwent invasive sampling. Although most of the proteins that changed significantly decreased from A to V, consistent with renal clearance, several were found to increase, the most significant of which was testican-2. To assess the clinical implications of these physiologic findings, we examined proteomic data in the Jackson Heart Study (JHS), an African-American cohort (n = 1,928), with replication in the Framingham Heart Study (FHS), a White cohort (n = 1,621). In both populations, testican-2 had a strong, positive correlation with estimated glomerular filtration rate (eGFR). In addition, higher baseline testican-2 levels were associated with a lower rate of eGFR decline in models adjusted for age, gender, hypertension, type 2 diabetes, body mass index, baseline eGFR, and albuminuria. Glomerular expression of testican-2 in human kidneys was demonstrated by immunohistochemistry, immunofluorescence, and electron microscopy, while single-cell RNA sequencing of human kidneys showed expression of the cognate gene, SPOCK2, exclusively in podocytes. In vitro, testican-2 increased glomerular endothelial tube formation and motility, raising the possibility that its secretion has a functional role within the glomerulus. Taken together, our findings identify testican-2 as a podocyte-derived biomarker of kidney health and prognosis.</p>}},
author = {{Ngo, Debby and Wen, Donghai and Gao, Yan and Keyes, Michelle J. and Drury, Erika R. and Katz, Dan H. and Benson, Mark D. and Sinha, Sumita and Shen, Dongxiao and Farrell, Laurie A. and Peterson, Bennet D. and Friedman, David J. and Elmariah, Sammy and Young, Bessie A. and Smith, J. Gustav and Yang, Qiong and Vasan, Ramachandran S. and Larson, Martin G. and Correa, Adolfo and Humphreys, Benjamin D. and Wang, Thomas J. and Pollak, Martin R. and Wilson, James G. and Gerszten, Robert E. and Rhee, Eugene P.}},
issn = {{1091-6490}},
keywords = {{chronic kidney disease; proteomics; testican-2}},
language = {{eng}},
number = {{40}},
pages = {{25026--25035}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences of the United States of America}},
title = {{Circulating testican-2 is a podocyte-derived marker of kidney health}},
url = {{http://dx.doi.org/10.1073/pnas.2009606117}},
doi = {{10.1073/pnas.2009606117}},
volume = {{117}},
year = {{2020}},
}