title: Relationship of clusterin with renal inflammation and fibrosis after the recovery phase of ischemia-reperfusion injury.
abstract: Long-term outcomes after acute kidney injury (AKI) include incremental loss of function and progression towards chronic kidney disease (CKD); however, the pathogenesis of AKI to CKD remains largely unknown. Clusterin (CLU) is a chaperone-like protein that reduces ischemia-reperfusion injury (IRI) and enhances tissue repair after IRI in the kidney. This study investigated the role of CLU in the transition of IRI to renal fibrosis.
  
  
  
  IRI was induced in the left kidneys of wild type (WT) C57BL/6J (B6) versus CLU knockout (KO) B6 mice by clamping the renal pedicles for 28 min at the body temperature of 32 °C. Tissue damage was examined by histology, infiltrate phenotypes by flow cytometry analysis, and fibrosis-related gene expression by PCR array.
  
  
  
  Reduction of kidney weight was induced by IRI, but was not affected by CLU KO. Both WT and KO kidneys had similar function with minimal cellular infiltration and fibrosis at day 14 of reperfusion. After 30 days, KO kidneys had greater loss in function than WT, indicated by the higher levels of both serum creatinine and BUN in KO mice, and exhibited more cellular infiltration (CD8 cells and macrophages), more tubular damage and more severe tissue fibrosis (glomerulopathy, interstitial fibrosis and vascular fibrosis). PCR array showed the association of CLU deficiency with up-regulation of CCL12, Col3a1, MMP9 and TIMP1 and down-regulation of EGF in these kidneys.
  
  
  
  Our data suggest that CLU deficiency worsens renal inflammation and tissue fibrosis after IRI in the kidney, which may be mediated through multiple pathways.
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.|Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Qiunong
authors.initials: Q
authors.lastname: Guan
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Xiuheng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.|Vancouver Prostate Centre, Vancouver, BC, Canada.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Gleave
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Christopher Y C
authors.initials: CY
authors.lastname: Nguan
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada. caigan@mail.ubc.ca.|Department of Urologic Sciences, The University of British Columbia, VGH-Jack Bell Research Centre, 2660 Oak St, Vancouver, BC, V6H 3Z6, Canada. caigan@mail.ubc.ca.
authors.forename: Caigan
authors.initials: C
authors.lastname: Du
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D051152:Clusterin / Q000172:deficiency*; D005355:Fibrosis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009393:Nephritis / Q000378:metabolism* / Q000473:pathology*; D020127:Recovery of Function / Q000502:physiology*; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology*
chemical_list: D015415:Biomarkers; C495243:Clu protein, mouse; D051152:Clusterin
keywords: Acute kidney injury; Chronic kidney disease; Clusterin; Fibrosis; Kidney ischemia-reperfusion