Suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the miR-23b/27b cluster.
Suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the miR-23b/27b cluster.
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通过 miR-23b/27b 簇下调 gremlin1 表达抑制肝星状细胞活化
DOI：
10.18632/oncotarget.13365
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发表时间：
2016-12-27
期刊：
影响因子：
--
通讯作者：
Liu CB
中科院分区：
文献类型：
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作者：
Zeng XY;Zhang YQ;He XM;Wan LY;Wang H;Ni YR;Wang J;Wu JF;Liu CB
在肝纤维化过程中，转化生长因子β和骨形态发生蛋白7信号通路之间的不平衡是促进肝星状细胞活化的关键步骤。Gremlin1可能会破坏平衡。gremlin1对肝星状细胞活化和肝纤维化的调控机制尚不清楚。在目前的研究中，gremlin1过表达可促进肝星状细胞的活化。用sirna敲低gremlin1可抑制大鼠肝星状细胞活化，减轻肝纤维化。我们的研究结果还表明，miR-23b/27b簇成员结合到gremlin1的3 ' -非翻译区，导致转化生长因子β、α-平滑肌肌动蛋白和胶原α1/2基因表达减少。我们的研究结果表明，gremlin1通过破坏转化生长因子β和骨形态发生蛋白7信号通路之间的平衡，促进肝星状细胞活化和肝纤维化。miR-23b/27b簇通过结合gremlin1来抑制肝星状细胞的激活，纠正这种不平衡。
The imbalance between transforming growth factor β and bone morphogenetic protein 7 signaling pathways is a critical step in promoting hepatic stellate cell activation during hepatic fibrogenesis. Gremlin1 may impair the balance. Something remains unclear about the regulatory mechanisms of gremlin1 action on hepatic stellate cell activation and hepatic fibrosis. In the current study, gremlin1 overexpression promotes activation of hepatic stellate cells. Knockdown of gremlin1 with siRNAs suppresses hepatic stellate cell activation and attenuates hepatic fibrosis in rat model. Our results also show that miR-23b/27b cluster members bind to 3′-untranslated region of gremlin1 resulting in reduction of transforming growth factor β, α-smooth muscle actin and collagenI α1/2 gene expression. Our findings suggest that gremlin1 promotes hepatic stellate cell activation and hepatic fibrogenesis through impairment of the balance between transforming growth factor β and bone morphogenetic protein 7 signaling pathways. The miR-23b/27b cluster suppresses activation of hepatic stellate cells through binding gremlin1 to rectify the imbalance.