15-Deoxy-Delta12,14-prostaglandin J2 regulates mesangial cell proliferation and death.
15-Deoxy-Delta12,14-prostaglandin J2 regulates mesangial cell proliferation and death.
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15-Deoxy-Delta12,14-prostaglandin J2 调节系膜细胞增殖和死亡。
DOI：
10.1046/j.1523-1755.2002.00282.x
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发表时间：
2002
影响因子：
19.6
通讯作者：
Hilbelink,Todd
中科院分区：
文献类型：
--
作者：
Rovin,BradH;Wilmer,WilliamA;Lu,Ling;Doseff,AndreaI;Dixon,Cynthia;Kotur,Mark;Hilbelink,Todd
15-脱氧-Δ12,14-前列腺素j2j调节系膜细胞增殖和死亡。肾小球内禀细胞增生是肾损伤的常见反应。急性时，增生可能是有益的，但损伤后持续的肾小球高细胞化与进行性肾衰竭有关。为了确定可能调控肾小球细胞数量的内源性因素，我们研究了j系列环戊酮前列腺素（pg）对人肾小球系膜细胞增殖和死亡的影响。方法在pgj22或其代谢物15-脱氧-Δ12,14-PGJ2（15dPGJ2）存在或不存在的情况下培养人系膜细胞。活细胞的数量是通过将四氮唑MTS还原成彩色的甲醛产物来测量的。凋亡通过caspase-3激活和DNA断裂来评估。结果spgj2at浓度达到10 μmol/L时可引起系膜增殖。15dpgj22在低浓度（≤2.5 μmol/L）下也能引起系膜细胞增殖，但在高浓度（≤5 μmol/L）下可引起系膜细胞死亡。在15dpgj2处理的细胞中，通过caspase-3活性和DNA片段的增加来测量细胞死亡的部分原因是凋亡。细胞死亡与生存因子Akt基线磷酸化水平下降和Akt降解增加有关，而15dpgj2诱导的系膜增殖可通过抑制PI 3-激酶/Akt通路而被阻断。15dpgj22是一种有效的PPARγ激动剂。与15dPGJ2一样，噻唑烷二酮型PPARγ配体（10 ~ 20 μmol/L）处理系膜细胞可导致细胞明显死亡，但在较低浓度下也可引起小程度的增殖。结论sj系列前列腺素可能通过akt依赖性增殖引发肾小球高细胞化，并通过ppar γ介导的细胞凋亡恢复正常肾小球结构。操纵这些前列腺素可能与进行性肾小球疾病的治疗有关。
15-Deoxy-Δ12,14-prostaglandin J2regulates mesangial cell proliferation and death.BackgroundProliferation of intrinsic glomerular cells is a common response to renal injury. Acutely, proliferation may be beneficial, but sustained glomerular hypercellularity after injury is associated with progressive renal failure. To identify endogenous factors that may be responsible for regulating glomerular cell number, the effects of J-series cyclopentenone prostaglandins (PGs) on human glomerular mesangial cell proliferation and death were examined.MethodsHuman mesangial cells were grown in the presence or absence of PGJ2or its metabolite 15-Deoxy-Δ12,14-PGJ2(15dPGJ2). The number of viable cells was measured by the reduction of the tetrazolium MTS to a colored formazan product. Apoptosis was assessed by caspase-3 activation and DNA fragmentation.ResultsPGJ2at concentrations up to 10 μmol/L caused mesangial proliferation. 15dPGJ2also caused mesangial proliferation at low concentrations (≤2.5 μmol/L), but induced mesangial cell death at higher concentrations (>5 μmol/L). Cell death occurred in part through apoptosis, measured as an increase in caspase-3 activity and DNA fragmentation in 15dPGJ2-treated cells. Cell death was associated with a decline in baseline phosphorylation of the survival factor Akt and increased Akt degradation, whereas 15dPGJ2-induced mesangial proliferation was blocked by inhibition of the PI 3-kinase/Akt pathway. 15dPGJ2is a potent PPARγ agonist. Like 15dPGJ2, treatment of mesangial cells with thiazolidinedione-type PPARγ ligands (10 to 20 μmol/L) caused significant cell death, but at lower concentrations also caused a small degree of proliferation.ConclusionsJ-series prostaglandins thus may be involved in the initiation of glomerular hypercellularity through Akt-dependent proliferation, and restoration of normal glomerular architecture through PPARγ-mediated apoptosis. Manipulation of these prostaglandins may be relevant to the treatment of progressive glomerular disease.