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Updated: Mar 11, 2026
Seven Steps to Stellate Cells
Published on: May 10, 2011
Suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the miR-23b/27b
Xian-Yi Zeng1,2,3, Yan-Qiong Zhang2,4, Xiao-Min He2,3
1The Institute of Cell Therapy, China Three Gorges University, Yichang, 443000, China.
Abstract:
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.
Insights
Gremlin1 drives hepatic fibrosis by disrupting TGF-β/BMP7 balance, activating hepatic stellate cells. MicroRNA-23b/27b counteracts this by targeting gremlin1, reducing fibrosis.
Area of Science:
- Molecular Biology
- Hepatology
- Fibrosis Research
Background:
- Hepatic fibrogenesis involves an imbalance in transforming growth factor β (TGF-β) and bone morphogenetic protein 7 (BMP7) signaling.
- Gremlin1 is implicated in impairing this crucial signaling balance.
- The precise regulatory mechanisms of gremlin1 in hepatic stellate cell activation and fibrosis remain unclear.
Purpose of the Study:
- To elucidate the role of gremlin1 in hepatic stellate cell activation and hepatic fibrosis.
- To investigate the regulatory mechanisms by which gremlin1 influences TGF-β/BMP7 signaling.
- To explore the potential of microRNA (miR) clusters in modulating gremlin1 activity.
Main Methods:
- Overexpression and siRNA-mediated knockdown of gremlin1 in hepatic stellate cells.
- Assessment of hepatic stellate cell activation markers.
- Evaluation of hepatic fibrosis in a rat model.
- Analysis of miR-23b/27b cluster binding to the 3'-untranslated region of gremlin1.
- Measurement of gene expression for TGF-β, α-smooth muscle actin, and collagen I α1/2.
Main Results:
- Gremlin1 overexpression significantly promoted hepatic stellate cell activation.
- Knockdown of gremlin1 suppressed hepatic stellate cell activation and attenuated hepatic fibrosis in vivo.
- The miR-23b/27b cluster directly binds to the gremlin1 3'-untranslated region, reducing key fibrotic gene expression.
Conclusions:
- Gremlin1 promotes hepatic stellate cell activation and hepatic fibrogenesis by disrupting the TGF-β/BMP7 signaling balance.
- The miR-23b/27b cluster acts as a suppressor of hepatic stellate cell activation by targeting gremlin1.
- Targeting gremlin1 or leveraging miR-23b/27b offers potential therapeutic strategies for hepatic fibrosis.
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