Mesangial Medium from IgA Nephropathy Patients Induces Podocyte Epithelial-to-mesenchymal Transition through Activation of the Phosphatidyl Inositol-3-kinase/Akt Signaling Pathway
Mesangial Medium from IgA Nephropathy Patients Induces Podocyte Epithelial-to-mesenchymal Transition through Activation of the Phosphatidyl Inositol-3-kinase/Akt Signaling Pathway
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IgA 肾病患者的系膜培养基通过激活磷脂酰肌醇 3 激酶/Akt 信号通路诱导足细胞上皮向间质转化
DOI：
10.1159/000170949
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发表时间：
2012-01-01
影响因子：
--
通讯作者：
Lou, Tanqi
中科院分区：
文献类型：
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作者：
Wang, Cheng;Liu, Xun;Lou, Tanqi
背景：足细胞损伤在IgA肾病（IgAN）的肾小球硬化过程中起着重要作用。由不同因素导致的上皮 - 间充质转化（EMT）是足细胞损伤的主要原因。本研究假设，经处理的系膜细胞条件培养基可能诱导足细胞发生EMT过程，进而导致肾小球损伤或硬化。
材料与方法：将足细胞置于与从IgAN患者分离出的聚集性IgA1（aIgA1）共同孵育的系膜细胞所产生的培养基中培养。使用渥曼青霉素抑制足细胞中的磷脂酰肌醇 - 3 - 激酶（PI3 - K）。
结果：蛋白质免疫印迹分析、实时荧光定量PCR以及共聚焦荧光显微镜检测显示，与在含0.5%胎牛血清（FBS）的RPMI 1640培养基中培养的足细胞相比，暴露于与从IgAN患者分离出的aIgA1共同孵育的系膜细胞所产生的培养基中的足细胞，其P - 钙黏蛋白、紧密连接蛋白 - 1（ZO - 1）和足细胞蛋白表达降低，成纤维细胞特异性蛋白（FSP - 1）、α - 平滑肌肌动蛋白（α - SMA）和结蛋白表达增加（p 此处p后面似乎缺少具体内容 ）
Background: Podocyte injury plays an important role in glomerulosclerosis in IgA nephropathy (IgAN). Eepithelial-to-mesenchymal transition (EMT) caused by different factors is the main reason for podocyte damage. This study hypothesized that conditioned mesangial medium may induced EMT process of podocytes and thereby lead to glomerular injury or sclerosis. Materials and Methods: Podocytes were incubated in medium from mesangial cells incubated with aggregated IgA1(aIgA1) isolated from IgAN patients. Wortmannin were used to inhibit phosphatidylinositol-3-kinase (PI3-K) in podocytes. Results: Western blot analysis, real-time PCR and confocal fluorescent microscopy demonstrated that reduced expression of P-Cadherin, Zonula occludens-1 (ZO-1) and podocin, increased expression of fibroblast –specific protein (FSP-1), α-smooth muscle action(α-SMA) and desmin in podocytes exposed to medium from mesangial cells incubated with aIgA1 isolated from IgAN patients compared with podocytes cultured in RPMI 1640 medium containing 0.5% fetal bovine serum ( FBS) (p<0.05). Mesangial medium resulted in a greater albumin influx across the podocyte monolayer (p<0.05). Phosphorylation of Akt increased with this medium, as indicated by an increase in the p-Akt/Akt ratio. Treatment with wortmannin partly restored the changes in epithelial and mesenchymal markers and albumin influx. IgAN patients with massive proteinuria showed remarkable α-SMA and FSP-1 expression in podocytes. Conclusion: Our findings indicated that mesangial medium from cells incubated with aIgA1 isolated from IgAN patients induced EMT in podocytes and the PI3-K/ Akt-signaling pathway was involved in the process.