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http://purl.uniprot.org/citations/33064897http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/33064897http://www.w3.org/2000/01/rdf-schema#comment"

Background

Endoplasmic reticulum (ER) perturbations are novel subcellular effectors involved in the ischaemia-reperfusion injury. As an ER stress-inducible protein, mesencephalic astrocyte-derived neurotrophic factor (MANF) has been proven to be increased during ischaemic brain injury. However, the role of MANF in liver ischaemia reperfusion (I/R) injury has not yet been studied.

Methods

To investigate the role of MANF in the process of liver ischaemia-reperfusion, Hepatocyte-specific MANF knockout (MANFhep-/- ) mice and their wild-type (WT) littermates were used in our research. Mice partial (70%) warm hepatic I/R model was established by vascular occlusion. We detected the serum levels of MANF in both liver transplant patients and WT mice before and after liver I/R injury. Recombinant human MANF (rhMANF) was injected into the tail vein before 1 hour occlusion. AST, ALT and Suzuki score were used to evaluate the extent of I/R injury. OGD/R test was performed on primary hepatocytes to simulate IRI in vitro. RNA sequence and RT-PCR were used to detect the cellular signal pathway activation while MANF knockout.

Results

We found that MANF expression and secretion are dramatically up-regulated during hepatic I/R. Hepatocyte-specific MANF knockout aggravates the I/R injury through the over-activated ER stress. The systemic administration of rhMANF before ischaemia has the potential to ameliorate I/R-triggered UPR and liver injury. Further study showed that MANF deficiency activated ATF4/CHOP and JNK/c-JUN/CHOP pathways, and rhMANF inhibited the activation of the two proapoptotic pathways caused by MANF deletion.

Conclusion

Collectively, our study unravels a previously unknown relationship among MANF, UPR and hepatic I/R injury."xsd:string
http://purl.uniprot.org/citations/33064897http://purl.org/dc/terms/identifier"doi:10.1111/liv.14697"xsd:string
http://purl.uniprot.org/citations/33064897http://purl.uniprot.org/core/author"Jiang T."xsd:string
http://purl.uniprot.org/citations/33064897http://purl.uniprot.org/core/author"Liu J."xsd:string
http://purl.uniprot.org/citations/33064897http://purl.uniprot.org/core/author"Shen Y."xsd:string
http://purl.uniprot.org/citations/33064897http://purl.uniprot.org/core/author"Zhang C."xsd:string
http://purl.uniprot.org/citations/33064897http://purl.uniprot.org/core/author"Wang P."xsd:string
http://purl.uniprot.org/citations/33064897http://purl.uniprot.org/core/author"Yang Y."xsd:string
http://purl.uniprot.org/citations/33064897http://purl.uniprot.org/core/author"Wei C."xsd:string
http://purl.uniprot.org/citations/33064897http://purl.uniprot.org/core/author"Huang F."xsd:string
http://purl.uniprot.org/citations/33064897http://purl.uniprot.org/core/author"Lv C."xsd:string
http://purl.uniprot.org/citations/33064897http://purl.uniprot.org/core/author"Shen Y.'"xsd:string
http://purl.uniprot.org/citations/33064897http://purl.uniprot.org/core/author"Chhetri G."xsd:string
http://purl.uniprot.org/citations/33064897http://purl.uniprot.org/core/author"Pang G."xsd:string
http://purl.uniprot.org/citations/33064897http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/33064897http://purl.uniprot.org/core/name"Liver Int"xsd:string
http://purl.uniprot.org/citations/33064897http://purl.uniprot.org/core/pages"623-639"xsd:string
http://purl.uniprot.org/citations/33064897http://purl.uniprot.org/core/title"Hepatocyte-derived MANF alleviates hepatic ischaemia-reperfusion injury via regulating endoplasmic reticulum stress-induced apoptosis in mice."xsd:string
http://purl.uniprot.org/citations/33064897http://purl.uniprot.org/core/volume"41"xsd:string
http://purl.uniprot.org/citations/33064897http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/33064897
http://purl.uniprot.org/citations/33064897http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/33064897
http://purl.uniprot.org/uniprot/#_A8C1V1-mappedCitation-33064897http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33064897
http://purl.uniprot.org/uniprot/#_A8K878-mappedCitation-33064897http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33064897
http://purl.uniprot.org/uniprot/#_P55145-mappedCitation-33064897http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33064897
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