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Circulating testica...
Circulating testican-2 is a podocyte-derived marker of kidney health
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- Ngo, Debby (author)
- Beth Israel Deaconess Medical Center
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- Wen, Donghai (author)
- Massachusetts General Hospital
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- Gao, Yan (author)
- University of Mississippi
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- Keyes, Michelle J. (author)
- Beth Israel Deaconess Medical Center
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- Drury, Erika R. (author)
- University of Rochester
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- Katz, Dan H. (author)
- Beth Israel Deaconess Medical Center
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- Benson, Mark D. (author)
- Beth Israel Deaconess Medical Center
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- Sinha, Sumita (author)
- Beth Israel Deaconess Medical Center
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- Shen, Dongxiao (author)
- Beth Israel Deaconess Medical Center
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- Farrell, Laurie A. (author)
- Beth Israel Deaconess Medical Center
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- Peterson, Bennet D. (author)
- Beth Israel Deaconess Medical Center
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- Friedman, David J. (author)
- Beth Israel Deaconess Medical Center
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- Elmariah, Sammy (author)
- Massachusetts General Hospital
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- Young, Bessie A. (author)
- University of Washington, Seattle,VA Puget Sound Health Care System
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- Smith, J. Gustav (author)
- Gothenburg University,Göteborgs universitet,University of Gothenburg,Lund University,Lunds universitet,Cardiovascular Epigenetics,Forskargrupper vid Lunds universitet,Lund University Research Groups,Sahlgrenska University Hospital,Skåne University Hospital,Wallenberglaboratoriet,Institutionen för medicin,Wallenberg Laboratory,Institute of Medicine
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- Yang, Qiong (author)
- Boston University
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- Vasan, Ramachandran S. (author)
- Boston University,National Heart Lung and Blood Institute
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- Larson, Martin G. (author)
- National Heart Lung and Blood Institute,Boston University
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- Correa, Adolfo (author)
- University of Mississippi
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- Humphreys, Benjamin D. (author)
- Washington University in St. Louis
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- Wang, Thomas J. (author)
- University of Texas Southwestern Medical Center
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- Pollak, Martin R. (author)
- Beth Israel Deaconess Medical Center
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- Wilson, James G. (author)
- Beth Israel Deaconess Medical Center
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- Gerszten, Robert E. (author)
- Beth Israel Deaconess Medical Center
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- Rhee, Eugene P. (author)
- Massachusetts General Hospital
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(creator_code:org_t)
- 2020-09-21
- 2020
- English 10 s.
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 117:40, s. 25026-25035
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https://www.pnas.org...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Keyword
- chronic kidney disease
- proteomics
- testican-2
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Ngo, Debby
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Wen, Donghai
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Gao, Yan
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Keyes, Michelle ...
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Drury, Erika R.
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Katz, Dan H.
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show more...
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Benson, Mark D.
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Sinha, Sumita
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Shen, Dongxiao
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Farrell, Laurie ...
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Peterson, Bennet ...
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Friedman, David ...
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Elmariah, Sammy
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Young, Bessie A.
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Smith, J. Gustav
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Yang, Qiong
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Vasan, Ramachand ...
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Larson, Martin G ...
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Correa, Adolfo
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Humphreys, Benja ...
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Wang, Thomas J.
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Pollak, Martin R ...
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Wilson, James G.
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Gerszten, Robert ...
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Rhee, Eugene P.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Urology and Neph ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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Proceedings of t ...
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Proceedings of t ...
- By the university
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Lund University
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University of Gothenburg