Department of Nephrology and Rheumatology, Children's Hospital of Fudan University Institutes of Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Nephrology (Carlton). 2012 Nov;17(8):669-75. doi: 10.1111/j.1440-1797.2012.01645.x.
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.
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 α-actinin-4.
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 α-actinin-4.
This study showed that dexamethasone had direct effects on podocytes: α-actinin-4 may be one of the potential target molecules.
自 20 世纪 50 年代以来，糖皮质激素治疗已应用于儿童肾病综合征，其特征性变化是肾小球足细胞的富含肌动蛋白的足突消失。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，还对足细胞具有直接作用，调节某些凋亡因子，并增加肌动蛋白丝的稳定性。然而，糖皮质激素对足细胞的保护作用的确切机制尚不清楚。已知阿霉素（ADR）可诱导足细胞足突消失，并在啮齿动物模型中引发大量蛋白尿。然而，很少有报道研究 ADR 在体外对足细胞肌动蛋白重排的直接作用。在这项研究中，我们研究了 ADR 如何直接诱导足细胞肌动蛋白细胞骨架重排，并进一步分析了地塞米松如何防止这种损伤。
我们使用共聚焦显微镜评估足细胞肌动蛋白重排。通过 Western blot 分析和实时聚合酶链反应测量α-辅肌动蛋白-4 的蛋白和 mRNA 水平。
我们证明了在培养的足细胞中，ADR 存在时间依赖性的诱导足细胞肌动蛋白重排，ADR 处理时间少于 12 小时。地塞米松可以保护足细胞免受 ADR 诱导的损伤，并且还可以稳定α-辅肌动蛋白-4 的表达。
这项研究表明，地塞米松对足细胞具有直接作用：α-辅肌动蛋白-4 可能是潜在的靶分子之一。
