PXD068822

PXD068822 is an original dataset announced via ProteomeXchange.

Title	The Circadian Clock Controls Hepatic Stellate Cell Activation in Liver Fibrosis via a BMAL1/CK1ε/REV-ERBα/Transgelin Signaling Pathway.
Description	Liver fibrosis is a progressive and life-threatening condition with no effective targeted treatments. Growing evidence indicates a two-way relationship between circadian rhythm and fibrogenesis, although the specific molecular signaling pathways involved are still not well understood. The molecular clock, which governs circadian rhythms, regulates metabolic and cellular functions, and its pharmacological manipulation has shown potential as a therapy for organ fibrosis. Although the liver's molecular clock appeared resilient to the progression of chronic liver disease in humans from steatosis to fibrosis, detectable changes in the daily amplitude of clock genes were observed in a cohort of people living with obesity. We discovered a clock-controlled signaling pathway that drives hepatic stellate cell (HSC) activation, a key event in fibrosis progression. Interfering with this pathway, either by disrupting the core regulator CLOCK:BMAL1 or activating the nuclear receptors REV-ERBs, significantly reduced HSC activation. We also identified transgelin as the downstream effector of clock-regulated HSC contractility, a characteristic of HSC activation. Transgelin is regulated indirectly by a BMAL1-CK1ε signaling pathway and directly by REV-ERBα. Our findings identify a previously unknown circadian-controlled mechanism that links the molecular clock to HSC activation and cell contractile function, which is relevant to human diseases. This pathway provides several entry points for drugs to target and disrupt fibrogenic signaling. By connecting clock biology to the cellular processes that cause fibrosis, our work also offers a mechanistic basis for chronotherapeutic strategies against chronic liver disease.
HostingRepository	PRIDE
AnnounceDate	2026-07-22
AnnouncementXML	Submission_2026-07-22_03:04:20.922.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD068822
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Didier Vertommen
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-25 01:51:29	ID requested
⏵ 1	2026-07-22 03:04:21	announced

10.6019/PXD068822;

10.1073/PNAS.2611767123;

submitter keyword: liver fibrosis, circadian clock

Philippe Lefebvre
contact affiliation	Inserm UMR1011, Bldg J&K Faculté de Médecine Henri Warembourg, Pôle Recherche Blvd du Prof Leclerc 59000, Lille, France
contact email	philippe-claude.lefebvre@inserm.fr
lab head
Didier Vertommen
contact affiliation	UCL - de Duve Institute, Brussels Belgium
contact email	didier.vertommen@uclouvain.be
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD068822
     1. Label: PRIDE project
     2. Name: The Circadian Clock Controls Hepatic Stellate Cell Activation in Liver Fibrosis via a BMAL1/CK1ε/REV-ERBα/Transgelin Signaling Pathway.