title: Role of WNT10A-expressing kidney fibroblasts in acute interstitial nephritis.
abstract: WNT signaling mediates various physiological and pathological processes. We previously showed that WNT10A is a novel angio/stromagenic factor involved in such processes as tumor growth, wound healing and tissue fibrosis. In this study, we investigated the role of WNT10A in promoting the fibrosis that is central to the pathology of acute interstitial nephritis (AIN). We initially asked whether there is an association between kidney function (estimated glomerular filtration rate; eGFR) and WNT10A expression using kidney biopsies from 20 patients with AIN. Interestingly, patients with WNT10A expression had significantly lower eGFR than WNT10A-negative patients. However, changes in kidney function were not related to the level of expression of other WNT family members. Furthermore, there was positive correlation between WNT10A and α-SMA expression. We next investigated the involvement of WNT10A in kidney fibrosis processes using COS1 cells, a kidney fibroblast cell line. WNT10A overexpression increased the level of expression of fibronectin and peroxiredoxin 5. Furthermore, WNT10A overexpression renders cells resistant to apoptosis induced by hydrogen peroxide and high glucose. Collectively, WNT10A may induce kidney fibrosis and associate with kidney dysfunction in AIN.
authors: Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; Second Department of Internal Medicine, Cardiology and Nephrology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors: Akihiro
authors: A
authors: Kuma
authors: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors: Sohsuke
authors: S
authors: Yamada
authors: Bio-information Research Center, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors: Ke-Yong
authors: KY
authors: Wang
authors: Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors: Noriaki
authors: N
authors: Kitamura
authors: Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors: Takahiro
authors: T
authors: Yamaguchi
authors: Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors: Yoshiko
authors: Y
authors: Iwai
authors: Department of Occupational Pneumology, Institute of Industrial Ecological Science, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors: Hiroto
authors: H
authors: Izumi
authors: Second Department of Internal Medicine, Cardiology and Nephrology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors: Masahito
authors: M
authors: Tamura
authors: Second Department of Internal Medicine, Cardiology and Nephrology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors: Yutaka
authors: Y
authors: Otsuji
authors: The President Laboratory, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors: Kimitoshi
authors: K
authors: Kohno
mesh_terms: D000199:Actins / Q000032:analysis / Q000235:genetics; D000208:Acute Disease; D000368:Aged; D017209:Apoptosis; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009395:Nephritis, Interstitial / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D018384:Oxidative Stress; D051153:Wnt Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D005353:Fibronectins; C484142:WNT10A protein, human; D051153:Wnt Proteins