title: Cell proliferation and apoptosis of the glomerular epithelial cells in rats with puromycin aminonucleoside nephrosis.
abstract: Injury and repair of the glomerular epithelial cells (GECs) play an important role in the pathogenesis of focal segmental glomerulosclerosis (FSGS). To obtain a better understanding of proliferation and apoptosis of GECs, we examined immunohistochemical and in situ hybridization findings in puromycin aminonucleoside nephrosis (PAN) of rats. The minimal-change nephrotic syndrome model (PAN-MCNS) was induced by administering 5 subcutaneous injections of puromycin aminonucleoside (PA; each 1.5 mg/100 g B/W to one group of rats), whereas the FSGS model (PAN-FSGS) was induced by administering an additional 5 injections of PA to another group of rats. The cell kinetics of the GECs were assessed with labeling 5-bromo 2'-deoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA). To investigate regulation of apoptosis in rats with PAN, we evaluated the expression of p53, Fas antigen, Fas ligand and Bc1-2. Rats with PAN-MCNS exhibited a significantly greater number of BrdU- and PCNA-labeled GECs as compared with control rats. In rats with PAN-FSGS, the number of PCNA-labeled GECs was greater than in rats with PAN-MCNS, but the number of BrdU-labeled GECs was lower. Apoptotic cells were occasionally observed in the sclerotic lesions, with the number being significantly higher in rats with PAN-FSGS than in rats with PAN-MCNS and control. Apoptotic cells were observed in the GECs of PAN-FSGS rats. However, they were negative for p53, Fas antigen, and Fas ligand. Immunohistochemical and in situ hybridization studies revealed a greater intraglomerular overexpression of Bc1-2 protein and bc1-2 mRNA in the PAN-FSGS rats as compared with control rats. These results suggest that insufficient proliferation and apoptosis in GECs may be involved in the progression of FSGS.
authors.affiliation: First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan. hshiiki@naramed-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Shiiki
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.forename: T
authors.initials: T
authors.lastname: Nishino
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: H
authors.initials: H
authors.lastname: Kurioka
authors.forename: S
authors.initials: S
authors.lastname: Fujimoto
authors.forename: K
authors.initials: K
authors.lastname: Dohi
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic; D017209:Apoptosis / Q000502:physiology*; D001973:Bromodeoxyuridine / Q000008:administration & dosage; D002455:Cell Division; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009401:Nephrosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D011692:Puromycin Aminonucleoside; D012313:RNA / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000903:Antibiotics, Antineoplastic; D011692:Puromycin Aminonucleoside; D012313:RNA; D001973:Bromodeoxyuridine