20-HETE and EETs in diabetic nephropathy: a novel mechanistic pathway.
20-HETE and EETs in diabetic nephropathy: a novel mechanistic pathway.
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DOI：
10.1371/journal.pone.0070029
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Eid AA
中科院分区：
文献类型：
--
作者：
Eid S;Maalouf R;Jaffa AA;Nassif J;Hamdy A;Rashid A;Ziyadeh FN;Eid AA
糖尿病肾病是糖尿病的主要并发症，以肥大、细胞外基质堆积、纤维化和蛋白尿为特征，导致肾功能丧失。肥大是导致近端肾小管上皮细胞损伤的主要因素。然而，导致肾小管损伤的机制还不是很清楚。在我们的研究中，我们发现大鼠近端肾小管上皮细胞暴露于高糖(HG)导致细胞外基质堆积和肥大增加。HG处理增加了ROS的产生，并伴随着20-HETE和EETS形成的改变而改变了细胞色素P4A和2C11的表达。HET0016可阻断HG诱导的肾小管损伤。相反，抑制EETs可促进HG对培养的近端肾小管细胞的作用。我们的结果还表明，Cyps 4A和2C表达的改变以及20HETE和EETs的形成调节了mTOR/p70S6Kinase通路的激活，该通路在糖尿病肾病的发生发展中起着重要作用。综上所述，我们认为糖尿病高血糖对花生四烯酸(AA)代谢产物的表达有显著影响，表现为AA代谢增加，从而可能通过改变AA代谢产物的种类和数量而改变肾功能。
Diabetic nephropathy (DN), a major complication of diabetes, is characterized by hypertrophy, extracellular matrix accumulation, fibrosis and proteinuria leading to loss of renal function. Hypertrophy is a major factor inducing proximal tubular epithelial cells injury. However, the mechanisms leading to tubular injury is not well defined. In our study, we show that exposure of rats proximal tubular epithelial cells to high glucose (HG) resulted in increased extracellular matrix accumulation and hypertrophy. HG treatment increased ROS production and was associated with alteration in CYPs 4A and 2C11 expression concomitant with alteration in 20-HETE and EETs formation. HG-induced tubular injury were blocked by HET0016, an inhibitor of CYPs 4A. In contrast, inhibition of EETs promoted the effects of HG on cultured proximal tubular cells. Our results also show that alteration in CYPs 4A and 2C expression and 20HETE and EETs formation regulates the activation of the mTOR/p70S6Kinase pathway, known to play a major role in the development of DN. In conclusion, we show that hyperglycemia in diabetes has a significant effect on the expression of Arachidonic Acid (AA)-metabolizing CYPs, manifested by increased AA metabolism, and might thus alter kidney function through alteration of type and amount of AA metabolites.
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细胞色素 P450 环氧化酶 CYP2J2 可减轻链脲佐菌素诱导的糖尿病小鼠的肾病。
DOI：
10.1016/j.prostaglandins.2011.06.009
发表时间：
2011-11-01
影响因子：
2.9
作者：
Chen, Guangzhi;Wang, Peihua;Wang, Dao Wen
通讯作者：
Wang, Dao Wen
影响因子：
19.6
作者：
Ha, HJ;Lee, HB
通讯作者：
Lee, HB
影响因子：
4.8
作者：
Eid, Assaad A.;Ford, Bridget M.;Abboud, Hanna E.
通讯作者：
Abboud, Hanna E.
DOI：
10.1073/pnas.081627898
发表时间：
2001-04-24
影响因子：
11.1
作者：
Holla, VR;Adas, F;Capdevila, JH
通讯作者：
Capdevila, JH
影响因子：
3.5
作者：
Jones, SC;Saunders, HJ;Pollock, CA
通讯作者：
Pollock, CA