miR-200b precursor can ameliorate renal tubulointerstitial fibrosis.
miR-200b precursor can ameliorate renal tubulointerstitial fibrosis.
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DOI：
10.1371/journal.pone.0013614
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发表时间：
2010-10-25
期刊：
影响因子：
3.7
通讯作者：
Fujita T
中科院分区：
文献类型：
--
作者：
Oba S;Kumano S;Suzuki E;Nishimatsu H;Takahashi M;Takamori H;Kasuya M;Ogawa Y;Sato K;Kimura K;Homma Y;Hirata Y;Fujita T
miR-200微rna （miRNAs）家族的成员已被证明可以抑制上皮-间质转化（EMT）。肾小管上皮细胞的EMT是肾成纤维细胞产生的机制。在这里，我们发现miR-200家族成员抑制转化生长因子- β (tgf - β)诱导的小管细胞EMT。单侧输尿管梗阻（UUO）是小管细胞EMT和随后的小管间质纤维化的常见模型。为了研究miR-200家族成员在小管间质纤维化中的作用，我们研究了它们在UUO小鼠肾脏中的表达。miR-200家族mirna的表达呈时间依赖性增加，其中miR-200b的诱导最为明显。为了阐明miR-200b在小管间质纤维化中的作用，我们静脉注射miR-200b前体。单次注射0.5 nM miR-200b前体足以抑制阻塞肾脏中I型胶原、III型胶原和纤维连接蛋白的增加，通过Azan染色观察肾脏证实纤维化改善。miR-200家族成员先前已被证明通过降低ZEB-1和ZEB-2的表达来抑制EMT， ZEB-1和ZEB-2是已知的E-cadherin的抑制因子。我们证明，在输尿管梗阻后，ZEB-1和ZEB-2的表达增加，并且给予miR-200b前体逆转了这种作用。综上所述，这些结果表明，miR-200家族在输尿管梗阻后上调，miR-200b被强烈诱导，miR-200b改善梗阻肾脏的小管间质纤维化。我们认为miR-200家族的成员，特别是miR-200b，可能构成肾脏疾病的新治疗靶点。
Members of the miR-200 family of micro RNAs (miRNAs) have been shown to inhibit epithelial-mesenchymal transition (EMT). EMT of tubular epithelial cells is the mechanism by which renal fibroblasts are generated. Here we show that miR-200 family members inhibit transforming growth factor-beta (TGF-beta)-induced EMT of tubular cells. Unilateral ureter obstruction (UUO) is a common model of EMT of tubular cells and subsequent tubulointerstitial fibrosis. In order to examine the role of miR-200 family members in tubulointerstitial fibrosis, their expression was investigated in the kidneys of UUO mice. The expression of miR-200 family miRNAs was increased in a time-dependent manner, with induction of miR-200b most pronounced. To clarify the effect of miR-200b on tubulointerstitial fibrosis, we injected miR-200b precursor intravenously. A single injection of 0.5 nM miR-200b precursor was sufficient to inhibit the increase of collagen types I, III and fibronectin in obstructed kidneys, and amelioration of fibrosis was confirmed by observation of the kidneys with Azan staining. miR-200 family members have been previously shown to inhibit EMT by reducing the expression of ZEB-1 and ZEB-2 which are known repressors of E-cadherin. We demonstrated that expression of ZEB-1 and ZEB-2 was increased after ureter obstruction and that administration of the miR-200b precursor reversed this effect. In summary, these results indicate that miR-200 family is up-regulated after ureter obstruction, miR-200b being strongly induced, and that miR-200b ameliorates tubulointerstitial fibrosis in obstructed kidneys. We suggest that members of the miR-200 family, and miR-200b specifically, might constitute novel therapeutic targets in kidney disease.
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影响因子：
14.9
作者：
Sun, YQ;Koo, S;Perera, RJ
通讯作者：
Perera, RJ
影响因子：
5
作者：
Kawai, Toru;Masaki, Takao;Yorioka, Noriaki
通讯作者：
Yorioka, Noriaki
DOI：
10.1016/j.bbrc.2008.04.097
发表时间：
2008-08-01
影响因子：
3.1
作者：
Mukai, Hidefumi;Kawakami, Shigeru;Hashida, Mitsuru
通讯作者：
Hashida, Mitsuru
影响因子：
11.2
作者：
Bracken, Cameron P.;Gregory, Philip A.;Goodall, Gregory J.
通讯作者：
Goodall, Gregory J.
影响因子：
13.2
作者：
KLAHR, S;ISHIDOYA, S;MORRISSEY, J
通讯作者：
MORRISSEY, J