α-Actinin-4 is involved in the process by which dexamethasone protects actin cytoskeleton stabilization from adriamycin-induced podocyte injury
α-Actinin-4 is involved in the process by which dexamethasone protects actin cytoskeleton stabilization from adriamycin-induced podocyte injury
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DOI：
10.1111/j.1440-1797.2012.01645.x
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发表时间：
2012-11-01
期刊：
影响因子：
2.5
通讯作者：
Zha, Xiliang
中科院分区：
文献类型：
--
作者：
Liu, Haimei;Gao, Xia;Zha, Xiliang
目的：自20世纪50年代以来，糖皮质激素治疗已被用于儿童肾病综合征，其特征性变化是肾小球足细胞富肌动蛋白足突的消失。最近的研究表明，糖皮质激素除了具有一般的免疫抑制和抗炎作用外，还直接作用于足细胞，调节一些凋亡因子，增加肌动蛋白丝的稳定性。然而，糖皮质激素对足细胞保护作用的确切机制尚不清楚。在啮齿类动物模型中，阿霉素（ADR）可诱导足细胞足突消失并引发大量蛋白尿。然而，很少有报道研究ADR在体外足细胞肌动蛋白重排中的直接作用。在本研究中，我们研究了ADR如何直接诱导足细胞肌动蛋白骨架重排，并进一步分析了地塞米松如何预防这种损伤。方法：用共聚焦显微镜观察足细胞肌动蛋白重排。采用Western blot和实时聚合酶链反应检测α - actiin -4蛋白和mRNA水平。结果：我们证明了ADR诱导的足细胞肌动蛋白重排在培养的足细胞中发生时间依赖性，ADR处理时间小于12小时。地塞米松能保护足细胞免受不良反应的损伤，并稳定α -肌动蛋白-4的表达。结论：本研究表明地塞米松对足细胞有直接作用，α -肌动素-4可能是其潜在的靶分子之一。
Aim: Glucocorticoid therapy has been used in childhood nephrotic syndrome since the 1950s, where the characteristic change is effacement of the actin-rich foot process of glomerular podocytes. Recent studies have shown that glucocorticoids, in addition to their general immunosuppressive and anti-inflammatory effects, have a direct effect on podocytes, regulate some apoptotic factors, and increase the stability of actin filaments. However, the precise mechanism(s) underlying the protective effects of glucocorticoids on podocytes remain unclear. It is known that adriamycin (ADR) can induce podocyte foot process effacement and trigger massive proteinuria in rodent models. However, few reports have examined the direct role of ADR in podocyte actin rearrangement in vitro. In this study, we investigated how ADR directly induced podocyte actin cytoskeleton rearrangement and further analyzed how dexamethasone prevented such injury.Methods: We used confocal microscopy to assess podocyte actin rearrangement. Western blot analysis and real-time polymerase chain reaction were performed to measure the protein and mRNA levels of alpha-actinin-4.Results: We demonstrated that there was a time-dependent ADR-induced podocyte actin rearrangement with less than 12 h of ADR treatment in cultured podocytes. Dexamethasone could protect podocytes from ADR-induced injury and also stabilize the expression of alpha-actinin-4.Conclusion: This study showed that dexamethasone had direct effects on podocytes: alpha-actinin-4 may be one of the potential target molecules.