title: OPN deficiency results in severe glomerulosclerosis in uninephrectomized mice.
abstract: Osteopontin (OPN) expression has been reported to be elevated in experimental models of renal injury such as arterial hypertension or diabetic nephropathy finally leading to focal segmental glomerulosclerosis (FSGS). FSGS is characterized by glomerular matrix deposition and loss or damage of podocytes that represent the main constituents of the glomerular filtration barrier. To evaluate the role of OPN in the kidney we investigated WT and OPN knockout mice (OPN-/-) without treatment, after uninephrectomy (UNX), as well as after UNX and desoxycorticosterone acetate (DOCA)-salt treatment with respect to urine parameters, glomerular morphology, and expression of podocyte markers. OPN-/- mice showed normal urine parameters while a thickening of the glomerular basement membrane was evident. Intriguingly, following UNX, OPN-/- mice exhibited prominent FSGS, proteinuria, and glomerular matrix deposition. Electron microscopy revealed bulgings of the glomerular basement membrane and occasionally an effacement of podocytes. After UNX and DOCA-salt treatment, severe glomerular lesions as well as proteinuria and albuminuria were seen in WT and OPN-/- mice. Moreover, we found a reduction of specific markers such as Wilm's tumor-1, podocin, and synaptopodin in both experimental groups indicating a loss of podocytes. Podocyte damage was accompanied by increased number of Ki-67-positive cells in the parietal epithelium of Bowman's capsule. We conclude that OPN plays a crucial role in adaptation of podocytes following renal ablation and is renoprotective when glomerular mechanical load is increased.
authors.affiliation: Department of Anatomy and Cell Biology, Universitätsmedizin Greifswald, Greifswald, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Schordan
authors.forename: Olaf
authors.initials: O
authors.lastname: Grisk
authors.forename: Eric
authors.initials: E
authors.lastname: Schordan
authors.forename: Bärbel
authors.initials: B
authors.lastname: Miehe
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Rumpel
authors.forename: Karlhans
authors.initials: K
authors.lastname: Endlich
authors.forename: Jürgen
authors.initials: J
authors.lastname: Giebel
authors.forename: Nicole
authors.initials: N
authors.lastname: Endlich
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000818:Animals; D001343:Autophagy; D003900:Desoxycorticosterone / Q000494:pharmacology; D050533:Glomerular Basement Membrane / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000473:pathology / Q000502:physiology*; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008262:Macrophage Activation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D009392:Nephrectomy; D053495:Osteopontin / Q000172:deficiency*; D050199:Podocytes / Q000473:pathology / Q000502:physiology*
chemical_list: D000199:Actins; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D053495:Osteopontin; D003900:Desoxycorticosterone
keywords: FSGS; nephrectomy; osteopontin; podocyte