title: Inhibition of WISE preserves renal allograft function.
abstract: 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.
authors.affiliation: Division of Metabolic Disorders Research, Amgen Inc, Thousand Oaks, California, USA. qianxm91377@gmail.com
authors.forename: Xueming
authors.initials: X
authors.lastname: Qian
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Yuan
authors.forename: Steven
authors.initials: S
authors.lastname: Vonderfecht
authors.forename: Xupeng
authors.initials: X
authors.lastname: Ge
authors.forename: Jae
authors.initials: J
authors.lastname: Lee
authors.forename: Anke
authors.initials: A
authors.lastname: Jurisch
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Andrew
authors.initials: A
authors.lastname: You
authors.forename: Vincent D
authors.initials: VD
authors.lastname: Fitzpatrick
authors.forename: Alexia
authors.initials: A
authors.lastname: Williams
authors.forename: Eliane G
authors.initials: EG
authors.lastname: Valente
authors.forename: Jim
authors.initials: J
authors.lastname: Pretorius
authors.forename: Jennitte L
authors.initials: JL
authors.lastname: Stevens
authors.forename: Barbara
authors.initials: B
authors.lastname: Tipton
authors.forename: Aaron G
authors.initials: AG
authors.lastname: Winters
authors.forename: Kevin
authors.initials: K
authors.lastname: Graham
authors.forename: Lindsey
authors.initials: L
authors.lastname: Harriss
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Baker
authors.forename: Michael
authors.initials: M
authors.lastname: Damore
authors.forename: Hossein
authors.initials: H
authors.lastname: Salimi-Moosavi
authors.forename: Yongming
authors.initials: Y
authors.lastname: Gao
authors.forename: Abdallah
authors.initials: A
authors.lastname: Elkhal
authors.forename: Chris
authors.initials: C
authors.lastname: Paszty
authors.forename: W Scott
authors.initials: WS
authors.lastname: Simonet
authors.forename: William G
authors.initials: WG
authors.lastname: Richards
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Tullius
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D015415:Biomarkers / Q000652:urine; D015820:Cadherins / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007668:Kidney / Q000276:immunology / Q000378:metabolism*; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D051437:Renal Insufficiency / Q000517:prevention & control* / Q000652:urine; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000199:Actins; D000906:Antibodies; D015415:Biomarkers; D015820:Cadherins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D051153:Wnt Proteins; D051176:beta Catenin; C473906:Sostdc1 protein, rat; C498862:Acta2 protein, rat