ELMO1 increases expression of extracellular matrix proteins and inhibits cell adhesion to ECMs
ELMO1 increases expression of extracellular matrix proteins and inhibits cell adhesion to ECMs
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DOI：
10.1038/sj.ki.5001939
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发表时间：
2006-11-01
影响因子：
19.6
通讯作者：
Maeda, S.
中科院分区：
文献类型：
--
作者：
Shimazaki, A.;Tanaka, Y.;Maeda, S.
我们之前已经确定吞噬和细胞运动1 （ELMO1）是糖尿病肾病的易感基因。为了阐明ELMO1在慢性肾损伤发病机制中的作用，我们检测了ELMO1在慢性肾小球肾炎大鼠模型（非肾切除加抗thy1 .1抗体[E30]注射）肾脏中的表达。我们发现，与对照组相比，未切除肾的大鼠注射E30后，肾皮质和肾小球中Elmo1的表达显著增加。通过原位杂交，Elmo1的表达在病变肾脏，尤其是肾小球上皮细胞中升高。在COS细胞中，ELMO1过表达导致纤维连接蛋白的表达显著增加，而在ELMO1过表达和对照细胞中，通过靶向ELMO1的小干扰RNA （small interfering RNA, siRNA）来消耗ELMO1可显著抑制纤维连接蛋白的表达。我们还发现，在ELMO1过表达的细胞中，integrin-linked kinase （ILK）的表达显著增加，而靶向ILK的siRNA部分但显著地抑制了ELMO1诱导的纤维连接蛋白的增加。此外，我们发现过表达ELMO1的细胞对ecm的粘附明显受到抑制。这些结果表明，ELMO1通过失调ECM代谢和降低细胞对ECM的粘附特性，参与慢性肾小球损伤的发生和进展。
We have previously identified the engulfment and cell motility 1 ( ELMO1) as a susceptibility gene for diabetic nephropathy. To elucidate the role of ELMO1 in the pathogenesis of chronic renal injury, we examined the expression of Elmo1 in the kidney of a rat model for chronic glomerulonephritis ( uninephrectomy plus anti-Thy1.1 antibody [ E30] injection). We found that the expression of the Elmo1 was significantly increased in the renal cortex and glomeruli of uninephrectomized rats injected with E30 compared to controls. By in situ hybridization, the expression of Elmo1 was shown to be elevated in the diseased kidney, especially in glomerular epithelial cells. In COS cells, the overexpression of ELMO1 resulted in a substantial increase in fibronectin expression, whereas the depletion of the ELMO1 by small interfering RNA ( siRNA) targeting ELMO1 significantly suppressed the fibronectin expression in ELMO1 overexpressing and control cells. We also found that the expression of integrin-linked kinase ( ILK) was significantly increased in ELMO1 overexpressing cells, and the ELMO1-induced increase in fibronectin was partially, but significantly, inhibited by siRNA targeting ILK. Furthermore, we identified that the cell adhesion to ECMs was considerably inhibited in cells overexpressing ELMO1. These results suggest that the ELMO1 contributes to the development and progression of chronic glomerular injury through the dysregulation of ECM metabolism and the reduction in cell adhesive properties to ECMs.