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- Title
Induction of p27[sup KIP1] after unilateral ureteral obstruction is independent of angiotensin II.
- Authors
Gerth, Jens H.; Kriegsmann, Jörg; Trinh, T. Tong; Stahl, Rolf A.K.; Wendt, Thoralf; Sommer, Manfred; Stein, Günter; Wolf, Gunter
- Abstract
Induction of p27[sup KIP1] after unilateral ureteral obstruction is independent of angiotensin II.. Background: Unilateral ureteral obstruction (UUO) is characterized by proliferation of tubular and interstitial cells, and infiltration of the renal parenchyma with macrophages/monocytes. These alterations lead ultimately to tubulointerstitial fibrosis and tubular atrophy. Some of these changes are caused by an activated renin-angiotensin system (RAS). We have previously demonstrated that angiotensin II induces the expression of the cell cycle inhibitor p27[sup KIP1] in cultured tubular cells. The current study tested the hypothesis that interference with the RAS may modulate renal expression of p27[sup KIP1] after UUO. Methods: The ureter of the left kidney of Sprague-Dawley rats was ligated. Sham-operated animals served as controls. Rats were randomized in four groups and received one of the following: no therapy, enalapril, losartan, or triple therapy (hydralazine, reserpine, hydrochlorothiazide). Kidneys were removed and cortical protein lysates were prepared for the detection of p27[sup KIP1] by Western blotting. Immunohistochemistry was performed for p27[sup KIP1], PCNA, ED-1, and α-smooth muscle actin. Apoptosis was quantified by TUNEL-staining. Results: p27[sup KIP1] expression as detected by Western blotting reached a maximum 10 days after UUO. Tubular and interstitial cells contributed to this increase in p27[sup KIP1] expression whereas the number of glomerular p27[sup KIP1] positive cell did not change. p27[sup KIP1]-positive cells were macrophages/monocytes (positive ED-1 staining) or had the characteristics of myofibroblasts (positive α-smooth muscle actin staining). Tubular and interstitial proliferation [proliferating cell nuclear antigen (PCNA)-positive staining] and apoptosis [terminal deoxy transferase uridine triphosphate nick end labeling (TUNEL) staining] also was increased after UUO. However, individual cells stained either p...
- Subjects
URETERIC obstruction; CELL proliferation; ANGIOTENSINS; PHYSIOLOGY
- Publication
Kidney International, 2002, Vol 61, Issue 1, p68
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2002.00111.x