Endoglin upregulation during experimental renal interstitial fibrosis in mice
Endoglin upregulation during experimental renal interstitial fibrosis in mice
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DOI：
10.1161/01.hyp.0000037429.73954.27
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发表时间：
2002-11-01
期刊：
影响因子：
8.3
通讯作者：
López-Novoa, JM
中科院分区：
文献类型：
--
作者：
Rodríguez-Peña, A;Eleno, N;López-Novoa, JM
本研究的目的是评价转化生长因子-β1(TGF-β1)辅助受体endoglin在肾纤维化发病机制中的作用。这是通过测试Enoglin杂合(Eng(+/-))小鼠单侧输尿管梗阻导致的肾小管间质纤维化模型来实现的。Northern和Western印迹分析表明，与Eng(+/+)小鼠相比，这些小鼠肾脏中endoglin的表达显著降低。通过Masson‘s三色染色和纤维连接蛋白、层粘连蛋白免疫组化染色的增强，在Eng(+/-)和Eng(+/+)小鼠之间，组织学证实了输尿管梗阻所致的显著间质纤维化。输尿管梗阻引起肾组织α2(I)和α1(IV)胶原、纤维连接蛋白和转化生长因子-β1(TGF-β1)mRNA水平显著升高，但Eng(+/-)和Eng(+/+)小鼠肾脏的变化相似。输尿管梗阻还诱导Eng(+/+)和Eng(+/-)小鼠的endoglin mRNA水平增加2倍，Western印迹分析证实这一点。因此，本研究提供了明确的证据表明，在单侧输尿管结扎诱导的间质纤维化小鼠的肾脏中，endoglin表达上调。然而，与正常小鼠相比，Eng(+/-)小鼠在此模型中诱导的肾脏疾病的严重程度没有任何变化，表明Enoglin的绝对水平对于转化生长因子-β1在肾脏纤维化过程中的作用并不是至关重要的。
The goal of the present study was to evaluate the role of endoglin, a transforming growth factor-beta1 (TGF-beta1) accessory receptor, in the pathogenesis of renal fibrosis. This was achieved by testing a model of tubulo-interstitial fibrosis induced by unilateral ureteral obstruction in endoglin heterozygous (Eng(+/-)) mice. Northern and Western blot analysis revealed that endoglin expression in kidneys of these mice was significantly reduced compared with Eng(+/+) littermates. Pronounced interstitial fibrosis induced by ureteral obstruction was confirmed histologically by Masson's trichromic staining and by increased immunostaining for fibronectin and laminin without significant differences between Eng(+/-) and Eng(+/+) mice. Ureteral obstruction induced significant increases in alpha2(I) and alpha1(IV) collagen, fibronectin, and TGF-beta1 mRNA levels, as well as in total kidney collagen but changes were similar in Eng(+/-) and Eng(+/+) mouse kidneys. Ureteral obstruction also induced a 2-fold increase in endoglin mRNA levels in both Eng(+/+) mice and Eng(+/-) mice, which was confirmed by Western blot analysis. Thus, the present study provides clear evidence that endoglin is upregulated in the kidneys of mice with interstitial fibrosis induced by unilateral ureteral ligation. However, Eng(+/-) mice do not show any changes in the severity of renal disease induced in this model when compared with normal mice, suggesting that the absolute level of endoglin is not critical for the effects of TGF-beta1 in the renal fibrosis process.