| Autor: |
Qian X; Division of Metabolic Disorders Research, Amgen Inc, Thousand Oaks, California, USA. qianxm91377@gmail.com, Yuan X, Vonderfecht S, Ge X, Lee J, Jurisch A, Zhang L, You A, Fitzpatrick VD, Williams A, Valente EG, Pretorius J, Stevens JL, Tipton B, Winters AG, Graham K, Harriss L, Baker DM, Damore M, Salimi-Moosavi H, Gao Y, Elkhal A, Paszty C, Simonet WS, Richards WG, Tullius SG |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2013 Jan; Vol. 24 (1), pp. 66-76. Date of Electronic Publication: 2012 Nov 26. |
| DOI: |
10.1681/ASN.2012010012 |
| Abstrakt: |
Wnt-modulator in surface ectoderm (WISE) is a secreted modulator of Wnt signaling expressed in the adult kidney. Activation of Wnt signaling has been observed in renal transplants developing interstitial fibrosis and tubular atrophy; however, whether WISE contributes to chronic changes is not well understood. Here, we found moderate to high expression of WISE mRNA in a rat model of renal transplantation and in kidneys from normal rats. Treatment with a neutralizing antibody against WISE improved proteinuria and graft function, which correlated with higher levels of β-catenin protein in kidney allografts. In addition, treatment with the anti-WISE antibody reduced infiltration of CD68(+) macrophages and CD8(+) T cells, attenuated glomerular and interstitial injury, and decreased biomarkers of renal injury. This treatment reduced expression of genes involved in immune responses and in fibrogenic pathways. In summary, WISE contributes to renal dysfunction by promoting tubular atrophy and interstitial fibrosis. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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