PXD035735

PXD035735 is an original dataset announced via ProteomeXchange.

Title	Secreted folate receptor-gamma drives fibrogenesis in nonalcoholic steatohepatitis by amplifying TGFβ signaling in hepatic stellate cells
Description	Hepatic fibrosis is the primary determinant of mortality in nonalcoholic steatohepatitis (NASH) patients. Antagonism of transforming growth factor  (TGF), a master profibrogenic cytokine, is a promising therapeutic target that has not yet been translated into an effective therapy, due in part to the lack of animal models resembling the human phenotype of NASH. Here we have identified that soluble secreted folate receptor gamma (FOLR3), expressed in humans but not rodents, is a secreted protein that is elevated in livers of NASH subjects but not in subjects with nonalcoholic fatty liver, type II diabetes, or healthy subjects. FOLR3, based on global proteomics, was the most highly expressed NASH-specific protein and positively correlated with increasing fibrosis stages, suggesting an impact on activated hepatic stellate cells (HSCs), the key fibrogenic cell in the liver. Exposure of stellate cells to exogenous FOLR3 led to elevated extracellular matrix (ECM) protein production, an effect synergistic with TGF1 Structurally, FOLR3 interacts with serine protease HTRA1, which downregulates TGFβ signaling through the degradation of its receptor TGFBR2. Administration of human FOLR3 to mice induced severe bridging fibrosis and an ECM pattern resembling human NASH. Our study uncovers a novel role of FOLR3 in enhancing fibrosis and identifies FOLR3 as a potential therapeutic target in NASH fibrosis
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_13:05:42.405.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD035735
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Carmen Merali
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-02 10:17:34	ID requested
⏵ 1	2025-05-06 13:05:43	announced

10.1126/scitranslmed.ade2966;

10.6019/PXD035735;

Quinn C, Rico MC, Merali C, Barrero CA, Perez-Leal O, Mischley V, Karanicolas J, Friedman SL, Merali S, signaling in hepatic stellate cells. Sci Transl Med, 15(715):eade2966(2023) [pubmed]

submitter keyword: proteomics,Nonalcoholic steatohepatitis, folate receptor gamma, transforming growth factor beta, hepatic stellate cells

Dr. Salim Merali
contact affiliation	Temple University School of Pharmacy, Department of Pharmaceutical Sciences
contact email	smerali@temple.edu
lab head
Carmen Merali
contact affiliation	Temple University
contact email	clmerali@temple.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035735
     1. Label: PRIDE project
     2. Name: Secreted folate receptor-gamma drives fibrogenesis in nonalcoholic steatohepatitis by amplifying TGFβ signaling in hepatic stellate cells