miRNA let-7e targeting MMP9 is involved in adipose-derived stem cell differentiation toward epithelia.
miRNA let-7e targeting MMP9 is involved in adipose-derived stem cell differentiation toward epithelia.
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DOI：
10.1038/cddis.2014.2
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发表时间：
2014-02-06
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
miRNA let-7 e参与干细胞分化，金属蛋白酶是其潜在的靶基因。我们推测let-7 e对MMP 9表达调控的抑制作用可能是脂肪干细胞（ASCs）分化过程中的一个重要机制。用全反式视黄酸（ATRA）分化ASC以促进分化，并测试分化期间let-7沉默的作用。结果表明，ASCs与ATRA培养分化成上皮细胞系。我们发现用ATRA培养或用miRNA let-7 e转染的ASCs表达上皮标记物如细胞角蛋白18和早期肾器官发生标记物如Pax 2、Wt 1、Wnt 4和megalin。相反，特异性敲除ASCs中的miRNA let-7 e显著降低了这些基因的表达，表明其在分化过程中的重要作用。使用荧光素酶报告基因分析，我们还表明MMP 9是miRNA let-7 e的直接靶点。因此，我们的研究结果表明，miRNA let-7 e作为基质金属蛋白酶9（MMP 9）抑制剂和分化诱导剂在ASCs。
miRNA let-7e is involved in stem cell differentiation, and metalloproteinases are among its potential target genes. We hypothesized that the inhibitory action of let-7e on regulation of MMP9 expression could represent a crucial mechanism during differentiation of adipose-derived stem cells (ASCs). ASCs were differentiated with all-trans retinoic acid (ATRA) to promote differentiation, and the effect of let-7 silencing during differentiation was tested. Results indicate that ASCs cultured with ATRA differentiated into cells of the epithelial lineage. We found that ASCs cultured with ATRA or transfected with miRNA let-7e expressed epithelial markers such as cytokeratin-18 and early renal organogenesis markers such as Pax2, Wt1, Wnt4 and megalin. Conversely, the specific knockdown of miRNA let-7e in ASCs significantly decreased the expression of these genes, indicating its vital role during the differentiation process. Using luciferase reporter assays, we also showed that MMP9 is a direct target of miRNA let-7e. Thus, our results suggest that miRNA let-7e acts as a matrix metalloproteinase-9 (MMP9) inhibitor and differentiation inducer in ASCs.
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影响因子：
5.2
作者：
Krichevsky, Anna M.;Sonntag, Kai-C.;Kosik, Kenneth S.
通讯作者：
Kosik, Kenneth S.
影响因子：
2.6
作者：
Goff, Loyal A.;Boucher, Shayne;Ricupero, Christopher L.;Fenstermacher, Sara;Swerdel, Mavis;Chase, Lucas G.;Adams, Christopher C.;Chesnut, Jonathan;Lakshmipathy, Uma;Hart, Ronald P.
通讯作者：
Hart, Ronald P.
DOI：
10.1083/jcb.136.6.1363
发表时间：
1997-03-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lelongt B;Trugnan G;Murphy G;Ronco PM
通讯作者：
Ronco PM
影响因子：
30.8
作者：
Chen, JF;Mandel, EM;Wang, DZ
通讯作者：
Wang, DZ
影响因子：
3.4
作者：
Heinzelmann, Joana;Henning, Brenda;Junker, Kerstin
通讯作者：
Junker, Kerstin