MCPIP1 Inhibits Hepatic Stellate Cell Activation in Autocrine and Paracrine Manners, Preventing Liver Fibrosis

MCPIP1通过自分泌和旁分泌方式抑制肝星状细胞活化,预防肝纤维化

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作者:Natalia Pydyn, Anna Ferenc, Katarzyna Trzos, Ewelina Pospiech, Mateusz Wilamowski, Olga Mucha, Piotr Major, Justyna Kadluczka, Pedro M Rodrigues, Jesus M Banales, Jose M Herranz, Matias A Avila, Tomasz Hutsch, Piotr Malczak, Dorota Radkowiak, Andrzej Budzynski, Jolanta Jura, Jerzy Kotlinowski0

Aims

Hepatic fibrosis is characterized by enhanced deposition of extracellular matrix (ECM), which

Background & aims

Hepatic fibrosis is characterized by enhanced deposition of extracellular matrix (ECM), which

Conclusions

We demonstrated that MCPIP1 is induced in human fibrotic livers and regulates the activation of HSCs in both autocrine and paracrine manners. Our results indicate that MCPIP1 could have a potential role in the development of liver fibrosis.

Methods

We analyzed MCPIP1 levels in patients' fibrotic livers and hepatic cells isolated from fibrotic murine livers. In vitro experiments were conducted on primary HSCs, cholangiocytes, hepatocytes, and LX-2 cells with MCPIP1 overexpression or silencing.

Results

MCPIP1 levels are induced in patients' fibrotic livers compared with their nonfibrotic counterparts. Murine models of fibrosis revealed that its level is increased in HSCs and hepatocytes. Moreover, hepatocytes with Mcpip1 deletion trigger HSC activation via the release of connective tissue growth factor. Overexpression of MCPIP1 in LX-2 cells inhibits their activation through the regulation of TGFB1 expression, and this phenotype is reversed upon MCPIP1 silencing. Conclusions: We demonstrated that MCPIP1 is induced in human fibrotic livers and regulates the activation of HSCs in both autocrine and paracrine manners. Our results indicate that MCPIP1 could have a potential role in the development of liver fibrosis.

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