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Key Event: 2414

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

COL3A1 Signaling Pathway

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
COL3A1 Signaling Pathway
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Molecular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Process Object Action
Hepatic bridging fibrosis increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
MPs & Cd induced inflammation-to-cancer transition in liver MolecularInitiatingEvent Wei Mu (send email) Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
Homo sapiens Homo sapiens High NCBI
mouse Mus musculus High NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
Not Otherwise Specified

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Unspecific

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

This key event is characterised by the abnormal transcriptional activation and protein upregulation of Collagen Type III Alpha 1 (COL3A1). As a core structural component of the extracellular matrix (ECM) in various organs, including the liver, the enrichment and activation of the COL3A1 signalling cascade serve as a critical molecular initiating signalling event that drives tissue remodelling and structural stiffening [1-3].

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

 Gene Expression Analysis (Transcriptional Level):

RT-qPCR (Reverse Transcription-Quantitative Polymerase Chain Reaction): Widely used to quantify the relative mRNA expression levels of the Col3a1 gene in tissue samples or cultured cells.

Transcriptomics (RNA-Seq / Microarray): High-throughput sequencing can detect the global enrichment of the COL3A1 pathway and related extracellular matrix (ECM)-receptor interaction gene sets via Gene Set Enrichment Analysis (GSEA) or KEGG pathway analysis.

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

The structural organization of Collagen Type III are known to be highly conserved throughout mammalian evolution[4].

References

List of the literature that was cited for this KE description. More help

1. Xu, Y., Mu, W., Li, J., Ba, Q., & Wang, H. (2021). Chronic cadmium exposure at environmental-relevant level accelerates the development of hepatotoxicity to hepatocarcinogenesis. Science of The Total Environment, 783. doi:10.1016/j.scitotenv.2021.146958

2. Li Y, Jian Y, Zhou J, Zhang M, Zhou Y, Ge Y, Wang H, Mu W. Molecular regulatory networks of microplastics and cadmium mediated hepatotoxicity from NAFLD to tumorigenesis via integrated approaches. Ecotoxicol Environ Saf. 2025 Jul 15;300:118431. doi: 10.1016/j.ecoenv.2025.118431.

3. Chen J, Ge J, Chen W, Zhao Y, Song T, Fu K, Li X, Zheng Y. UPLC-Q-TOF-MS based investigation into the bioactive compounds and molecular mechanisms of Lamiophlomis Herba against hepatic fibrosis. Phytomedicine. 2023 Dec;121:155085. doi: 10.1016/j.phymed.2023.155085. Epub 2023 Sep 16. PMID: 37757709.

4.Gelse K, Pöschl E, Aigner T. Collagens--structure, function, and biosynthesis. Adv Drug Deliv Rev. 2003 Nov 28;55(12):1531-46. doi: 10.1016/j.addr.2003.08.002. PMID: 14623400.