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Background & aims

Hepatic stellate cells activation is the key process of liver fibrosis, revealing the molecular mechanism of which is helpful to provide an effective target for inhibiting liver fibrosis. Rab31, a small GTPase, regulates the specificity of intracellular vesicular transport system, and is crucial for signal transduction. However, whether Rab31 is involved in hepatic stellate cells activation is unknown.

Methods & results

Analysis of the differences in gene expression between human healthy and fibrotic liver tissues by sequencing revealed that Rab31 was significantly upregulated in fibrotic tissues. Immunohistochemistry and immunofluorescence analysis confirmed that Rab31 positively correlated with hepatic fibrosis. Next, mouse primary hepatic stellate cells were prepared, and their continuous activation was accompanied by Rab31 expression increased. Interestingly, knockdown of Rab31 by lentivirus can significantly restrict those cell activation. Subsequently, the vary of signal transduction after Rab31 knockdown was detected, its presented that the TGF-β/Smads signaling was obviously affected. Following experiments identified that Rab31 knockdown significantly inhibited the TGF-β activation and led to the failure of hepatic stellate cells activation. Importantly, we revealed that Rab31 knockdown could inhibit TGF-β receptor II complex endocytosis, a prerequisite for the activation of TGF-β signaling. Finally, in a mouse CCl4 fibrosis model, we proved that Rab31 knockdown markedly inhibited hepatic fibrosis.

Conclusions

Our study demonstrated that Rab31 could promote hepatic stellate cells activation by accelerating TGF-β Receptor II complex endocytosis, suggesting that interfering with Rab31 could be an effectively strategy to inhibit hepatic fibrosis progression."xsd:string
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http://purl.uniprot.org/citations/35091093http://purl.uniprot.org/core/author"He S."xsd:string
http://purl.uniprot.org/citations/35091093http://purl.uniprot.org/core/author"Huang S."xsd:string
http://purl.uniprot.org/citations/35091093http://purl.uniprot.org/core/author"Liu Y."xsd:string
http://purl.uniprot.org/citations/35091093http://purl.uniprot.org/core/author"Zhong L."xsd:string
http://purl.uniprot.org/citations/35091093http://purl.uniprot.org/core/author"Qiu C."xsd:string
http://purl.uniprot.org/citations/35091093http://purl.uniprot.org/core/author"Ning B."xsd:string
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http://purl.uniprot.org/citations/35091093http://purl.uniprot.org/core/title"Rab31 promotes activation of hepatic stellate cells by accelerating TGF-beta receptor II complex endocytosis."xsd:string
http://purl.uniprot.org/citations/35091093http://purl.uniprot.org/core/volume"144"xsd:string
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