title: Reduced postischemic macrophage infiltration and interstitial fibrosis in osteopontin knockout mice.
abstract: BACKGROUND
  Osteopontin (OPN) is a phosphoprotein that is up-regulated in several experimental models of renal disease, including ischemia/reperfusion injury. OPN has been described as a macrophage chemoattractant, may serve as a survival factor for tubular cells, and is implicated in the development of tubulointerstitial fibrosis. However, the precise role of this protein in renal pathophysiology remains unclear.
  
  
  METHODS
  OPN knockout and wild-type mice were subjected to 30 minutes of warm renal ischemia combined with a contralateral nephrectomy, and sacrificed at six different time points, ranging from 12 hours to seven days after reperfusion. Besides functional and morphological parameters of postischemic acute renal failure (ARF), macrophage infiltration, apoptosis and expression of collagen types I and IV were investigated.
  
  
  RESULTS
  Postischemic ARF in OPN knockouts and wild-types showed a similar course and severity, without significant differences in either functional or morphological disease parameters. However, macrophage infiltration was significantly diminished in OPN knockouts after five and seven days, in cortex as well as in the outer stripe of the outer medulla (OSOM). Furthermore, OPN knockout mice showed significantly enhanced apoptosis in the injury phase and significantly less collagen I and IV expression in the regeneration phase of postischemic ARF.
  
  
  CONCLUSIONS
  There was no influence of OPN protein on the severity or course of functional impairment or morphological injury in the first seven days after an ischemic insult to the kidney. However, our results demonstrate that OPN favors macrophage recruitment to the postischemic kidney, inhibits apoptosis, and stimulates the development of renal fibrosis after an acute ischemic insult.
authors.affiliation: Department of Nephrology, University of Antwerp, Belgium.
authors.forename: Veerle P
authors.initials: VP
authors.lastname: Persy
authors.forename: Anja
authors.initials: A
authors.lastname: Verhulst
authors.forename: Dirk K
authors.initials: DK
authors.lastname: Ysebaert
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: De Greef
authors.forename: Marc E
authors.initials: ME
authors.lastname: De Broe
mesh_terms: D000818:Animals; D017209:Apoptosis; D001831:Body Temperature; D024042:Collagen Type I / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D005355:Fibrosis; D007150:Immunohistochemistry / Q000379:methods; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology; D008264:Macrophages / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D053495:Osteopontin; D012038:Regeneration; D012079:Renal Circulation; D012795:Sialoglycoproteins / Q000172:deficiency*; D013194:Staining and Labeling
chemical_list: D024042:Collagen Type I; D024141:Collagen Type IV; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin