Shiiki H, Sasaki Y, Nishino T, Kimura T, Kurioka H, Fujimoto S, Dohi K
First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan.
Pathobiology. 1998;66(5):221-9. doi: 10.1159/000028027.
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.
肾小球上皮细胞（GECs）的损伤与修复在局灶节段性肾小球硬化症（FSGS）的发病机制中起着重要作用。为了更好地了解GECs的增殖和凋亡情况，我们检测了大鼠嘌呤霉素氨基核苷肾病（PAN）的免疫组化和原位杂交结果。通过给一组大鼠皮下注射5次嘌呤霉素氨基核苷（PA；每次1.5mg/100g体重）诱导微小病变肾病综合征模型（PAN-MCNS），而通过给另一组大鼠额外注射5次PA诱导FSGS模型（PAN-FSGS）。用5-溴-2'-脱氧尿苷（BrdU）和增殖细胞核抗原（PCNA）标记来评估GECs的细胞动力学。为了研究PAN大鼠凋亡的调控，我们评估了p53、Fas抗原、Fas配体和Bcl-2的表达。与对照大鼠相比，PAN-MCNS大鼠中BrdU和PCNA标记的GECs数量显著更多。在PAN-FSGS大鼠中，PCNA标记的GECs数量多于PAN-MCNS大鼠，但BrdU标记的GECs数量较少。在硬化病变中偶尔观察到凋亡细胞，PAN-FSGS大鼠中的凋亡细胞数量显著高于PAN-MCNS大鼠和对照大鼠。在PAN-FSGS大鼠的GECs中观察到了凋亡细胞。然而，它们的p53、Fas抗原和Fas配体呈阴性。免疫组化和原位杂交研究显示，与对照大鼠相比，PAN-FSGS大鼠肾小球内Bcl-2蛋白和bcl-2 mRNA的过表达更高。这些结果表明，GECs增殖和凋亡不足可能参与了FSGS的进展。
