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Multimodal decoding of human liver regeneration [snrna_mouse]

ABSTRACT: Multimodal decoding of human liver regeneration [snrna_mouse]

PROVIDER: PRJNA927115 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23200629.fastq.gz	Fastqsanger.gz
	SRR23200630.fastq.gz	Fastqsanger.gz
	SRR23200631.fastq.gz	Fastqsanger.gz
	SRR23200632.fastq.gz	Fastqsanger.gz
	SRR23200633.fastq.gz	Fastqsanger.gz

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Project description:The liver is the only organ in mammals, which fully regenerates after injury. To identify novel regulators of liver regeneration, we performed quantitative large-scale proteomics analysis of subcellular fractions from normal versus regenerating mouse liver. Proteins of the ubiquitin-proteasome pathway were rapidly regulated by partial hepatectomy, with the ubiquitin ligase Nedd4-1 being among the top hits. Knock-down of Nedd4-1 in hepatocytes in vivo through nanoparticle-mediated delivery of siRNA caused severe liver damage after partial hepatectomy and impaired regeneration, resulting in liver failure. Mechanistically, we demonstrate that Nedd4-1 is required for efficient activation of Erk1/2 signaling by receptor tyrosine kinases involved in liver regeneration through inhibition of receptor internalization, thus controlling a major pro-mitogenic and cytoprotective signaling pathway in the regenerating liver. These results highlight the power of large-scale proteomics to identify key players in liver regeneration and the importance of posttranslational regulation of growth factor signaling in this process.

2017-09-13 | PXD004108 | Pride

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