Augmenting podocyte injury promotes advanced diabetic kidney disease in Akita mice.
Augmenting podocyte injury promotes advanced diabetic kidney disease in Akita mice.
复制标题
加重荚膜细胞损伤会促进秋田小鼠晚期糖尿病肾病的发生。
DOI：
10.1016/j.bbrc.2014.01.115
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发表时间：
2014-02-21
影响因子：
3.1
通讯作者：
Spurney, Robert F.
中科院分区：
文献类型：
--
作者：
Wang, Liming;Tang, Yuping;Eisner, William;Sparks, Matthew A.;Buckley, Anne F.;Spurney, Robert F.
为了确定增强足细胞损伤是否促进晚期糖尿病肾病（DN）的发展，我们建立了在糖尿病秋田小鼠（Akita-CD小鼠）足细胞中特异性表达胞嘧啶脱氨酶（CD）的小鼠。在这些小鼠中，用前药5-氟胞嘧啶（5-FC）治疗导致足细胞损伤，这是由于转化为毒性代谢物5-氟尿嘧啶（5-FU）。我们发现，与不表达CD（秋田CTL）的5-FC处理秋田对照组相比，用5-FC处理4-5周龄秋田小鼠5天在16和20周龄时引起了大量白蛋白尿。到20周龄时，与秋田CTL相比，秋田CD小鼠的系膜扩张显著增加，这与肾小球基底膜（GBM）宽度和间质纤维化的可变增加相关。在20周龄时，足细胞数量在两组秋田小鼠中相似地减少，并且与蛋白尿和系膜扩张呈负相关。因此，在疾病过程的早期增强足细胞损伤促进显著的系膜扩张、间质纤维化、GBM厚度增加和强烈的白蛋白尿的发展。这些数据表明，足细胞在糖尿病肾病晚期特征的发展中起关键作用。
To determine if augmenting podocyte injury promotes the development of advanced diabetic nephropathy (DN), we created mice that expressed the enzyme cytosine deaminase (CD) specifically in podocytes of diabetic Akita mice (Akita-CD mice). In these mice, treatment with the prodrug 5-flucytosine (5-FC) causes podocyte injury as a result of conversion to the toxic metabolite 5-fluorouracil (5-FU). We found that treatment of 4-5 week old Akita mice with 5-FC for 5 days caused robust albuminuria at 16 and 20 weeks of age compared to 5-FC treated Akita controls, which do not express CD (Akita CTLs). By 20 weeks of age, there was a significant increase in mesangial expansion in Akita-CD mice compared to Akita CTLs, which was associated with a variable increase in glomerular basement membrane (GBM) width and interstitial fibrosis. At 20 weeks of age, podocyte number was similarly reduced in both groups of Akita mice, and was inversely correlated with the albuminuria and mesangial expansion. Thus, enhancing podocyte injury early in the disease process promotes the development of prominent mesangial expansion, interstitial fibrosis, increased GBM thickness and robust albuminuria. These data suggest that podocytes play a key role in the development of advanced features of diabetic kidney disease.
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影响因子：
13.6
作者：
Pichaiwong, Warangkana;Hudkins, Kelly L.;Alpers, Charles E.
通讯作者：
Alpers, Charles E.
影响因子：
7.7
作者：
Dalla Vestra, M;Masiero, A;Fioretto, P
通讯作者：
Fioretto, P
DOI：
10.1159/000342369
发表时间：
2012
期刊：
Nephron. Experimental nephrology
影响因子：
--
作者：
Wang L;Tang Y;Howell DN;Ruiz P;Spurney RF
通讯作者：
Spurney RF
影响因子：
13.6
作者：
Ronconi, Elisa;Sagrinati, Costanza;Romagnani, Paola
通讯作者：
Romagnani, Paola
影响因子：
158.5
作者：
Lewis, EJ;Hunsicker, LG;Raz, I
通讯作者：
Raz, I