Sano H, Asano K, Minatoguchi S, Hiraoka J, Fujisawa K, Nishigaki K, Yasuda N, Kumada H, Takemura M, Ohashi H, Seishima M, Fujiwara T, Fujiwara H
2nd Department of Internal Medicine, Gifu University School of Medicine, Gifu Prefectural Hospital, Gifu, Japan.
Nephron. 1998 Oct;80(2):153-61. doi: 10.1159/000045159.
It has been reported that glomerular cells with apoptosis and positive Fas immunoreactivity are seen in proliferative glomerulonephritis (PGN). Fas induces apoptosis when it binds to Fas ligand (Fas-L) or soluble Fas-L (sFas-L). However, soluble Fas (sFas) blocks apoptosis by inhibiting binding between Fas and Fas-L or sFas-L. That is, Fas, Fas-L, and sFas-L are inducers of apoptosis, but sFas is an inhibitor of apoptosis. We studied the relationship between the plasma levels of sFas and sFas-L in 32 patients with various types of adult chronic glomerulonephritis. Patients with serum creatinine levels >1.5 mg/dl (132.6 micromol/l) were excluded. The plasma levels of sFas-L were within the normal limits in all patients. The plasma levels of sFas in the patients with minimal-change (n = 8) and membranous nephropathy (n = 7) were similar to the age- and sex-matched controls. However, the plasma sFas levels were significantly elevated in patients with mesangial PGN (n = 10) and membranoproliferative glomerulonephritis (n = 7)(3. 4 +/- 0.9 and 3.9 +/- 1.5 ng/ml, respectively) as compared with the age- and sex-matched controls (controls: 2.1 +/- 0.4 and 2.2 +/- 0.6 ng/ml, respectively). In PGN, according to increase of histological grade and decrease of creatinine clearance, the number of TUNEL-positive cells in glomeruli is decreased in spite of an increase of the Fas positivity, and plasma sFas is increased. The degree of proliferative change is determined by the balance between proliferation and apoptosis and/or necrosis. Therefore, increased plasma sFas in PGN may inhibit apoptosis in glomeruli and may be one of the progressing factors in PGN. Thus, we conclude that an increase in plasma sFas levels is important to the protection of apoptosis in PGN.
据报道，在增殖性肾小球肾炎（PGN）中可见具有凋亡和Fas免疫反应阳性的肾小球细胞。Fas与Fas配体（Fas-L）或可溶性Fas-L（sFas-L）结合时会诱导凋亡。然而，可溶性Fas（sFas）通过抑制Fas与Fas-L或sFas-L之间的结合来阻断凋亡。也就是说，Fas、Fas-L和sFas-L是凋亡诱导剂，但sFas是凋亡抑制剂。我们研究了32例不同类型成人慢性肾小球肾炎患者血浆sFas和sFas-L水平之间的关系。血清肌酐水平>1.5mg/dl（132.6微摩尔/升）的患者被排除。所有患者的血浆sFas-L水平均在正常范围内。微小病变（n = 8）和膜性肾病（n = 7）患者的血浆sFas水平与年龄和性别匹配的对照组相似。然而，与年龄和性别匹配的对照组（对照组：分别为2.1±0.4和2.2±0.6ng/ml）相比，系膜增生性PGN（n = 10）和膜增生性肾小球肾炎（n = 7）患者的血浆sFas水平显著升高（分别为3.4±0.9和3.9±1.5ng/ml）。在PGN中，根据组织学分级的增加和肌酐清除率的降低，尽管Fas阳性增加，但肾小球中TUNEL阳性细胞的数量减少，血浆sFas增加。增殖性变化的程度由增殖与凋亡和/或坏死之间的平衡决定。因此，PGN中血浆sFas的增加可能会抑制肾小球中的凋亡，并且可能是PGN进展的因素之一。因此，我们得出结论，血浆sFas水平的升高对PGN中凋亡的保护很重要。
