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Sökning: onr:"swepub:oai:lup.lub.lu.se:93f3ae6f-1176-43dd-9e46-3373b4250428" > Circulating testica...

Circulating testican-2 is a podocyte-derived marker of kidney health

Ngo, Debby (författare)
Beth Israel Deaconess Medical Center
Wen, Donghai (författare)
Massachusetts General Hospital
Gao, Yan (författare)
University of Mississippi
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Keyes, Michelle J. (författare)
Beth Israel Deaconess Medical Center
Drury, Erika R. (författare)
University of Rochester
Katz, Dan H. (författare)
Beth Israel Deaconess Medical Center
Benson, Mark D. (författare)
Beth Israel Deaconess Medical Center
Sinha, Sumita (författare)
Beth Israel Deaconess Medical Center
Shen, Dongxiao (författare)
Beth Israel Deaconess Medical Center
Farrell, Laurie A. (författare)
Beth Israel Deaconess Medical Center
Peterson, Bennet D. (författare)
Beth Israel Deaconess Medical Center
Friedman, David J. (författare)
Beth Israel Deaconess Medical Center
Elmariah, Sammy (författare)
Massachusetts General Hospital
Young, Bessie A. (författare)
VA Puget Sound Health Care System,University of Washington, Seattle
Smith, J. Gustav (författare)
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,Institutionen för medicin,Wallenberglaboratoriet,Institute of Medicine,Wallenberg Laboratory
Yang, Qiong (författare)
Boston University
Vasan, Ramachandran S. (författare)
National Heart Lung and Blood Institute,Boston University
Larson, Martin G. (författare)
Boston University,National Heart Lung and Blood Institute
Correa, Adolfo (författare)
University of Mississippi
Humphreys, Benjamin D. (författare)
Washington University in St. Louis
Wang, Thomas J. (författare)
University of Texas Southwestern Medical Center
Pollak, Martin R. (författare)
Beth Israel Deaconess Medical Center
Wilson, James G. (författare)
Beth Israel Deaconess Medical Center
Gerszten, Robert E. (författare)
Beth Israel Deaconess Medical Center
Rhee, Eugene P. (författare)
Massachusetts General Hospital
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 (creator_code:org_t)
2020-09-21
2020
Engelska 10 s.
Ingår i: 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
Relaterad länk:
http://dx.doi.org/10...
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https://www.pnas.org...
https://lup.lub.lu.s...
https://doi.org/10.1...
https://gup.ub.gu.se...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

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)

Nyckelord

chronic kidney disease
proteomics
testican-2

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