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Chitinase-like protein Brp-39/YKL-40 modulates the renal response to ischemic injury and predicts delayed allograft function.
- Source :
-
Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2013 Feb; Vol. 24 (2), pp. 309-19. Date of Electronic Publication: 2013 Jan 04. - Publication Year :
- 2013
-
Abstract
- Kidney hypoperfusion during episodes of systemic hypotension or after surgical procurement for transplantation can lead to tubular cell death via necrosis and apoptosis, which trigger a series of responses that promote repair. The factors that contribute to the repair phase after kidney injury are not well understood. Using a urine proteomic screen in mice, we identified the macrophage-secreted chitinase-like protein Brp-39, the murine protein product of the chitinase 3-like 1 gene, as a critical component of this reparative response that serves to limit tubular cell apoptotic death via activation of Akt, improving animal survival after kidney ischemia/reperfusion. Examination of graded times of renal ischemia revealed a direct correlation between the degree of kidney injury and both Chi3l1/Brp-39 expression in the kidney and its levels in the urine. In samples collected from patients undergoing deceased-donor kidney transplantation, we found higher levels of the orthologous human protein, YKL-40, in urine and blood from allografts subjected to sufficient peri-transplant ischemia to cause delayed graft function than from allografts with slow or immediate graft function. Urinary levels of YKL-40 obtained within hours of transplant predicted the need for subsequent dialysis in these patients. In summary, these data suggest that Brp-39/YKL-40 is a sensor of the degree of injury, a critical mediator of the reparative response, and a possible biomarker to identify patients at greatest risk of sustained renal failure after transplantation.
- Subjects :
- Adipokines genetics
Animals
Apoptosis physiology
Biomarkers blood
Biomarkers urine
Cells, Cultured
Chitinase-3-Like Protein 1
Delayed Graft Function mortality
Delayed Graft Function physiopathology
Disease Models, Animal
Epithelial Cells cytology
Glycoproteins genetics
Humans
Kidney cytology
Lectins genetics
Macrophages metabolism
Male
Mice
Mice, Inbred C57BL
Phosphatidylinositol 3-Kinases metabolism
Predictive Value of Tests
Proto-Oncogene Proteins c-akt metabolism
Reperfusion Injury mortality
Reperfusion Injury physiopathology
Signal Transduction physiology
Transplantation, Homologous
Adipokines metabolism
Delayed Graft Function metabolism
Glycoproteins metabolism
Kidney Transplantation
Lectins metabolism
Reperfusion Injury metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1533-3450
- Volume :
- 24
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of the American Society of Nephrology : JASN
- Publication Type :
- Academic Journal
- Accession number :
- 23291472
- Full Text :
- https://doi.org/10.1681/ASN.2012060579