PXD030956-3

PXD030956 is an original dataset announced via ProteomeXchange.

Title	Murine liver tolerates repeated toxic injuries through microsteatosis and mild inflammation
Description	The liver has a remarkable capacity to regenerate and thus compensates for repeated injuries through toxic chemicals, drugs, alcohol, or malnutrition for decades. However, largely unknown is how and when alterations in the liver occur due to tolerable damaging insults. To that end, we induced repeated liver injuries over ten weeks in a mouse model injecting carbon tetrachloride (CCl4) twice a week. We lost 10% of the study animals within the first six weeks, which was accompanied by a steady deposition of extracellular matrix (ECM) regardless of metabolic activity of the liver. From week six onwards, all mice survived, and in these mice ECM deposition was rather reduced suggesting ECM remodelling as a liver response contributing to better coping with repeated injuries. The data of time-resolved paired transcriptome and proteome profiling of 18 mice was subjected to multi-level network inference, using Knowledge guided Multi-Omics Network inference (KiMONo), identified multi-level key markers exclusively associated with the injury-tolerant liver response. Interestingly, pathways of cancer and inflammation were lighting up and were validated using independent data sets compiled of 1034 samples from publicly available human cohorts. Interestingly, a yet undescribed link to lipid metabolism in this damage-tolerant phase was identified. Immunostaining revealed an unexpected accumulation of small lipid droplets (microvesicular steatosis) in parallel to a recovery of catabolic processes of the liver to pre-injury levels. Further, mild inflammation was experimentally validated. Taken together, we identified week six as a critical time point to switch the liver response program from an acute response that fosters ECM accumulation to a tolerant “survival” phase with pronounced deposition of small lipid droplets in hepatocytes potentially protecting against the repetitive injury with toxic chemicals. Our data suggest that microsteatosis formation plus a mild inflammatory state represent biomarkers and probably functional liver requirements to resist chronic damage.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:57:14.934.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alexander Held
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-14 03:43:21	ID requested
1	2023-07-21 01:44:56	announced
2	2023-11-14 09:04:06	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 05:57:15	announced	2024-10-22: Updated project metadata.

10.1038/s41419-023-05855-4;

Hammad S, Ogris C, Othman A, Erdoesi P, Schmidt-Heck W, Biermayer I, Helm B, Gao Y, Pioro, ń, ska W, Holland CH, D'Alessandro LA, de la Torre C, Sticht C, Al Aoua S, Theis FJ, Bantel H, Ebert MP, Klingm, ü, ller U, Hengstler JG, Dooley S, Mueller NS, Tolerance of repeated toxic injuries of murine livers is associated with steatosis and inflammation. Cell Death Dis, 14(7):414(2023) [pubmed]

submitter keyword: Multi-Omics, Liver fibrosis, Integrative data analysis, liver damage adaptation, CCl4, Tolerance, KiMONo

Prof. Dr. Ursula Klingmüller
contact affiliation	Head of Division 'Systems Biology of Signal Transduction' German Cancer Research Center (DKFZ), Heidelberg, Germany (lab head)
contact email	u.klingmueller@dkfz.de
lab head
Alexander Held
contact affiliation	DKFZ Heidelberg
contact email	a.gorol@dkfz.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/07/PXD030956

PRIDE project URI

• PRIDE
  1. PXD030956
     1. Label: PRIDE project
     2. Name: Murine liver tolerates repeated toxic injuries through microsteatosis and mild inflammation