Diabetes Induced Changes in Podocyte Morphology and Gene Expression Evaluated Using GFP Transgenic Podocytes.
Diabetes Induced Changes in Podocyte Morphology and Gene Expression Evaluated Using GFP Transgenic Podocytes.
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DOI：
10.7150/ijbs.13057
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发表时间：
2016
影响因子：
9.2
通讯作者：
Epstein PN
中科院分区：
文献类型：
--
作者：
Xu J;Zheng S;Kralik PM;Krishnan L;Huang H;Hoying JB;Cai L;Carlson EC;Tan Y;Epstein PN
糖尿病在体内的影响尚未在分离的足细胞上进行检查。为了实现这一点，GFP在PGFP转基因小鼠的足细胞中组成型表达，所述PGFP转基因小鼠与OVE小鼠繁殖以产生糖尿病OVE-GFP小鼠。观察GFP荧光，OVE-GFP足细胞的足突在视觉上和可测量地消失，这在不太严重的STZ糖尿病中没有发生。从每只PGFP小鼠纯化超过300，000个足细胞，但每只糖尿病OVE-GFP小鼠仅纯化49，000个足细胞。来自OVE-GFP小鼠的低产量似乎是由于大多数OVE-GFP糖尿病足细胞的更脆弱状态，其不能在分离过程中存活。分离的糖尿病足细胞具有高水平的脂质过氧化产物4-HNE，它们对氧化应激引起的死亡更敏感。OVE-GFP足细胞的基因阵列分析显示参与炎症的基因的强烈糖尿病诱导。四种CXC趋化因子被诱导至少3倍，并且首次显示趋化因子CXCL 1在足细胞中被OVE、dbdb和STZ糖尿病特异性诱导。
The effect of diabetes in vivo has not been examined on isolated podocytes. To achieve this, GFP was expressed constitutively in podocytes of PGFP transgenic mice which were bred to OVE mice to produce diabetic OVE-GFP mice. Viewing GFP fluorescence, foot processes of OVE-GFP podocytes were visually and measurably effaced, which did not occur with less severe STZ diabetes. Over 300,000 podocytes were purified from each PGFP mouse but only 49,000 podocytes per diabetic OVE-GFP mouse. The low yield from OVE-GFP mice appeared to be due to more fragile state of most OVE-GFP diabetic podocytes which did not survive the isolation process. Diabetic podocytes that were isolated had high levels of the lipid peroxidation product 4-HNE and they were more sensitive to death due to oxidative stress. Gene array analysis of OVE-GFP podocytes showed strong diabetes induction of genes involved in inflammation. Four CXC chemokines were induced at least 3-fold and the chemokine CXCL1 was shown for the first time to be specifically induced in podocytes by OVE, dbdb and STZ diabetes.