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Comment
. 2023 Nov 1;78(5):1329-1331.
doi: 10.1097/HEP.0000000000000455. Epub 2023 May 16.

The pre-mRNA alternative splicing regulated by SRPK2: A new player in alcohol-associated liver disease?

Zhihong Yang  1 , Wen-Xing Ding  2   3
Affiliations
Comment

The pre-mRNA alternative splicing regulated by SRPK2: A new player in alcohol-associated liver disease?

Zhihong Yang et al. Hepatology. .
No abstract available

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Conflict of interest statement

Conflict of interest: None of the authors have any conflicts of interest with this work.

Figures

Fig. 1.
Fig. 1.. Regulation of pre-mRNA alternative splicing by FGF21/SRPK2 in alcohol-associated liver disease.
Alcohol consumption induces stabilization and activation of the splicing kinase SRPK2 via the mTORC1 signaling pathway. Elevated SRPK2 interacts with SRSF10, leading to impaired alternative splicing of Lipin 1 pre-mRNA, which leads to increased exon 7 inclusion and generates the Lipin 1β isoform. Subsequently, Lipin 1β may activate the transcriptional factor SREBP-1 by not yet known mechanisms and enhance the expression of lipogenic genes resulting in alcoholic steatosis and hepatoxicity. Notably, overexpression of FGF21 attenuates the pathogenesis of ALD by inhibiting mTORC1-mediated SRPK2 protein stability and its downstream effects.
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