H Liapis1, H Yu, G F Steinhardt. 1. Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Abstract
PURPOSE: Complete ureteral obstruction (CUTO) in the fetal kidney induces tubular and glomerular cysts, interstitial fibrosis, and halts renal development. Previous studies have shown that apoptosis is a predominant mechanism in the chronically injured kidney following obstruction, but the precise cellular and molecular mechanisms are poorly understood. MATERIALS AND METHODS: We have used CUTO in opossum pups with early metanephric kidneys, sacrificed at two weeks, to evaluate the role of cell proliferation, apoptosis and apoptosis regulating genes, Bcl-2 and Bax. RESULTS: Obstructed fetal kidneys demonstrate high apoptosis in the renal pelvis and tubulointerstitium, compared with sham operated animals. Apoptosis is accompanied by statistically significant increased cell proliferation in the interstitium but not in tubules. Apoptosis in the tubules is accompanied by increased Bax and decreased Bcl-2 staining. In the nephrogenic zone apoptosis is increased, even though it is not statistically significant. Bcl-2 and Bax in the nephrogenic zone are unchanged compared with sham, but cell proliferation is increased. CONCLUSIONS: We suggest that abnormal patterns of cell kinetics may contribute to disease pathogenesis in the obstructed fetal kidney.
PURPOSE: Complete ureteral obstruction (CUTO) in the fetal kidney induces tubular and glomerular cysts, interstitial fibrosis, and halts renal development. Previous studies have shown that apoptosis is a predominant mechanism in the chronically injured kidney following obstruction, but the precise cellular and molecular mechanisms are poorly understood. MATERIALS AND METHODS: We have used CUTO in opossum pups with early metanephric kidneys, sacrificed at two weeks, to evaluate the role of cell proliferation, apoptosis and apoptosis regulating genes, Bcl-2 and Bax. RESULTS: Obstructed fetal kidneys demonstrate high apoptosis in the renal pelvis and tubulointerstitium, compared with sham operated animals. Apoptosis is accompanied by statistically significant increased cell proliferation in the interstitium but not in tubules. Apoptosis in the tubules is accompanied by increased Bax and decreased Bcl-2 staining. In the nephrogenic zone apoptosis is increased, even though it is not statistically significant. Bcl-2 and Bax in the nephrogenic zone are unchanged compared with sham, but cell proliferation is increased. CONCLUSIONS: We suggest that abnormal patterns of cell kinetics may contribute to disease pathogenesis in the obstructed fetal kidney.
Authors: Nikesh Thiruchelvam; Peter Nyirady; Donald M Peebles; Christopher H Fry; Peter M Cuckow; Adrian S Woolf Journal: Am J Pathol Date: 2003-04 Impact factor: 4.307