PXD033550

PXD033550 is an original dataset announced via ProteomeXchange.

Title	Hepatocyte thorns, a novel drug-induced stress response in human and mouse liver spheroids
Description	The in vivo-relevant phenotype of 3D liver spheroids allows for long-term studies of e.g. novel mechanisms of chronic drug-induced liver toxicity. Using this system, we present a novel drug-induced stress response in human and murine hepatocyte spheroids wherein long slender filaments form after chronic treatment with four different drugs, of which, three are PPARα an-tagonists. The morphology of the thorns varies between donors and compounds used. They are mainly composed of diverse protein fibres, which are glycosylated. Their formation is inhibited by treatment with fatty acids or antioxidants. Treatment of mice with GW6471, revealed changes in gene and protein expression like those in the spheroids. In addition, similar changes in kera-tin expression were seen following treatment of hepatotoxic drugs including aflatoxin B1, para-cetamol, chlorpromazine, cyclosporine and ketoconazole. We suggest that thorn formation may be indicative of hepatocyte metaplasia in response to toxicity and that more focus should be placed on alterations of ECM derived protein expression as biomarkers of liver disease and chronic drug-induced hepatotoxicity, changes that can be studied in stable in vivo-like hepatic cell systems like the spheroids.
HostingRepository	PRIDE
AnnounceDate	2022-05-26
AnnouncementXML	Submission_2022-05-26_05:58:52.232.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Massimiliano Gaetani
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-28 02:30:16	ID requested
⏵ 1	2022-05-26 05:58:52	announced

Dataset with its publication pending

submitter keyword: Hepatocytes

Spheroids

Thorns

Hepatotoxicity

Keratins

3D culture

Massimiliano Gaetani
contact affiliation	Chemical Proteomics, Division of Physiological Chemistry I, MBB Department, Biomedicum, Karolinska Institute, 17177 Stockholm
contact email	massimiliano.gaetani@ki.se
lab head
Massimiliano Gaetani
contact affiliation	Karolinska Institutet
contact email	massimiliano.gaetani@ki.se
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/2022/05/PXD033550

PRIDE project URI

• PRIDE
  1. PXD033550
     1. Label: PRIDE project
     2. Name: Hepatocyte thorns, a novel drug-induced stress response in human and mouse liver spheroids