Effects of cyclosporine in osteopontin null mice1

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Effects of cyclosporine in osteopontin null mice1 Marilda Mazzali, Jeremy Hughes, Marcio Dantas, Lucy Liaw, Susan Steitz, Charles E. Alpers, Raimund H. Pichler, Hui Y. Lan, Cecilia M. Giachelli, Stuart J. Shankland, William G. Couser, Richard J. Johnson Kidney International Volume 62, Issue 1, Pages 78-85 (July 2002) DOI: 10.1046/j.1523-1755.2002.00408.x Copyright © 2002 International Society of Nephrology Terms and Conditions

Figure 1 Osteopontin (OPN) was up-regulated in cyclosporine (CsA) nephropathy in OPN+/+ mice and was expressed in preglomerular arterial vessels. Tubular expression of OPN was increased in both cortical and medullary areas in OPN+/+ mice treated with CsA for 2 weeks (B) compared to untreated OPN+/+ mice (A). The histological findings of CsA nephropathy (tubular atrophy and dilatation, striped fibrosis and afferent arteriolar hyalinosis (C) was similar in both OPN+/+ and OPN-/- mice. However, OPN+/+ mice showed increased incidence of afferent arteriolar hyalinosis and expression of OPN in afferent arterioles (arrow) (D). (A and B, immunohistochemistry for osteopontin, magnification ×50; C, PAS staining, ×50; D, osteopontin staining, ×1000). Kidney International 2002 62, 78-85DOI: (10.1046/j.1523-1755.2002.00408.x) Copyright © 2002 International Society of Nephrology Terms and Conditions

Figure 2 The lack of OPN was associated with less interstitial cell proliferation and macrophage infiltration. The number of proliferating BrdU positive cells (arrows) in interstitial renal cortex (arrows) was reduced in OPN-/- mice (A) compared to OPN+/+ (B). The interstitial cell proliferation correlated directly with the degree of macrophage infiltration (C and D). A and B, double staining FX1A/BrdU, ×640 (BrdU+ cells stained in black, proximal tubular brush border stained in brown); C shows macrophage infiltration, F4/80 staining, ×200). Symbols in D are: (○) OPN-/- control; (•) OPN+/+ control; (⋄) OPN-/- 2 weeks; (⋄) OPN+/+ 2 weeks. Kidney International 2002 62, 78-85DOI: (10.1046/j.1523-1755.2002.00408.x) Copyright © 2002 International Society of Nephrology Terms and Conditions