Xing Yan, Ding Jie, Fan Qingfeng, Guan Na
Department of Pediatrics, Peking University First Hospital, Beijing, People's Republic of China.
Exp Biol Med (Maywood). 2006 May;231(5):585-93. doi: 10.1177/153537020623100513.
Nephrin, podocin, CD2AP, and alpha-actinin-4 are important podocyte proteins that help maintain the integrity of the slit diaphragm and prevent proteinuria. Studies have shown that angiotensin-converting enzyme inhibitors, glucocorticoids, and all-trans retinoic acid (ATRA) have antiproteinuric effects. However, it is still unclear whether these drugs, with different pharmacological mechanisms, lead to a reduction in proteinuria by changing the expression and distribution of these important podocyte proteins. In this study, changes in the expression and distribution of nephrin, podocin, CD2AP, and alpha-actinin-4 were dynamically detected in Adriamycin-induced nephrotic (ADR) rats treated with three different drugs: lisinopril, prednisone, and ATRA. Nephropathy was induced by an intravenous injection of Adriamycin. After Adriamycin injection, rats received lisinopril, prednisone, and ATRA treatment, respectively. Renal tissues were collected at Days 3, 7, 14, and 28. The distribution and the expression of messenger RNA and protein of nephrin, podocin, CD2AP, and alpha-actinin-4 were detected by indirect immunofluorescence, real-time polymerase chain reaction, and Western blotting, respectively. With the intervention of lisinopril, prednisone, and ATRA, changes in the expression of nephrin, podocin, and CD2AP were diverse, which was different from that detected in ADR rats. After lisinopril and prednisone intervention, podocin exhibited prominent earlier changes compared with those of nephrin and CD2AP, whereas CD2AP showed more prominent changes after ATRA intervention. There was no change in the expression of alpha-actinin-4 molecule. In summary, we conclude that the antiproteinuric effects of lisinopril, prednisone, and ATRA were achieved by changes in the expression and distribution of the important podocyte molecules nephrin, podocin, CD2AP, and alpha-actinin-4. The pattern in the change of podocyte molecules after lisinopril and prednisone intervention was similar, but the pattern in the change of podocyte molecules after ATRA intervention was different from that of lisinopril or prednisone intervention.
Nephrin、足突蛋白、CD2相关蛋白（CD2AP）和α辅肌动蛋白-4是重要的足细胞蛋白，有助于维持裂孔隔膜的完整性并预防蛋白尿。研究表明，血管紧张素转换酶抑制剂、糖皮质激素和全反式维甲酸（ATRA）具有抗蛋白尿作用。然而，这些具有不同药理机制的药物是否通过改变这些重要足细胞蛋白的表达和分布来降低蛋白尿仍不清楚。在本研究中，动态检测了用三种不同药物（赖诺普利、泼尼松和ATRA）治疗的阿霉素诱导的肾病（ADR）大鼠中Nephrin、足突蛋白、CD2AP和α辅肌动蛋白-4的表达和分布变化。通过静脉注射阿霉素诱导肾病。注射阿霉素后，大鼠分别接受赖诺普利、泼尼松和ATRA治疗。在第3、7、14和28天收集肾组织。分别通过间接免疫荧光、实时聚合酶链反应和蛋白质印迹法检测Nephrin、足突蛋白、CD2AP和α辅肌动蛋白-4的信使核糖核酸和蛋白质的分布及表达。随着赖诺普利、泼尼松和ATRA的干预，Nephrin、足突蛋白和CD2AP的表达变化多样，这与ADR大鼠中检测到的情况不同。在赖诺普利和泼尼松干预后，与Nephrin和CD2AP相比，足突蛋白表现出更明显的早期变化，而在ATRA干预后CD2AP表现出更明显的变化。α辅肌动蛋白-4分子的表达没有变化。总之，我们得出结论，赖诺普利、泼尼松和ATRA的抗蛋白尿作用是通过重要足细胞分子Nephrin、足突蛋白、CD2AP和α辅肌动蛋白-4的表达和分布变化实现的。赖诺普利和泼尼松干预后足细胞分子的变化模式相似，但ATRA干预后足细胞分子的变化模式与赖诺普利或泼尼松干预的不同。
