Lung fibrosis (Homo sapiens)

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GTPaseactivatorELMOD28MIE - Molecular Initiating EventAE - Associative Event KE4 (KE:1500) - Increased, fibroblast proliferation and myofibroblast differentiationAE2 - Cellular toxicity, cell deathKE3 (KE:1499) - Increased, activation of T (T) helper (h) type 2 cellsAE1 - Increase of reactive oxygen species levelsKE5 (KE:1501) - Increased, extracellular matrix depositionKE2 (KE:1497) - Increased, recruitment of inflammatory cellsKE1 (KE:1496) - Increased, secretion of proinflammatory and profibrotic mediatorsMIE (KE:1495) - Interaction with the lung resident cell membrane componentsAO (KE:1458) - Pulmonary fibrosisKE - Key EventAO - Adverse OutcomeChemokine signalingCollagen productonStressfibre assemblyChondrocytedifferentiationMatrixmetalloproteinases67DifferentiationPathwayNRF2signalingTGF betasignalingCytokinesand inflammatoryresponseApoptosis22GPCRsignalingRegulation ofreactive oxygen speciesmetabolismPulmonary fibrosisFibroblastproliferation, resistance to apoptosis, differentiationinto myofibroblasts, collagen productionPulmonary surfactantproteinsExcess deposition and/or reduced turnover of extracellular matrix (ECM)Macrophage-relatedoxidative stressandinflammasome activationMIE9SalivarysecretionEpithelial injury andapoptosis:disturbed interactionwith mesenchymal cells,epithelial-mesenchymaltransition TelomereorganizationSerine-typepeptidase activityLeukocyte/Myeloid celldifferentiationIntermediatefilamentcytoskeletonMethylation/chromatin bindingLung injury (known or unknown) combined with tissue response (normal or abnormal)2RTEL1CXCL2SPP1DPP9FGF1CCL4SMAD7TERCCTGFSFTPA2PARNMAPKsignalingCCL2SERPINA1SKILTNFSFTPA1IL6Oxidative StressEDN1ELNCSF3GREM1Inflammasomeactivation3DSPTERTMECP2CXCL8OBFC1CALCATGFAIL13IL1BCCR3CCL5PDGFANADPHoxidaseCCL11ATP11AFGF2InflammationCMA1IL5Coagulation disturbancesEGFTIMP1NF-KBIL12BBMP7PDGFBPTX3NFE2L2MMP9FGF7MUC5BCEBPBCYSLTR2HMOX1p38 MAPKMMP2HGFSFTPCCCR2IL4CSF2PLAUFAM13ACCL3MT2AIGF1TGFB1ROSproduction3Additional non-connected genes with direct association topulmonary fibrosis in the Comparative Toxicogenomics Database (CTD)5All genes in the network are directly associated withpulmonary fibrosis in the Comparative Toxicogenomics Database (CTD)4, 5ROSproduction3NF-KBKE1/KE2Inflammasomeactivation93KE19KE1/KE39KE1/KE39KE1/KE29KE3/KE49KE39KE3/KE49KE39KE49KE49KE59AO9AE19AE19AE19AE29AE19KE3/KE49KE3/KE49KE39Events related to the Adverse Outcome Pathway forpulmonary fibrosis (AOP:173)9LegendToll-like receptorsignalingAE3AE3 - Collagen production- (KE:1498) - Loss of alveolar capillary membrane integrity8


Description

Lung fibrosis pathway linked to events (molecular initiating event, key events and associative events) in a putative Adverse Outcome Pathway for lung fibrosis.


Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

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Ontology Terms

 

Bibliography

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  1. Todd NW, Luzina IG, Atamas SP; ''Molecular and cellular mechanisms of pulmonary fibrosis.''; http://www.ncbi.nlm.nih.gov/pubmed/22824096, 2012 PubMed Europe PMC Scholia
  2. Vietti G, Lison D, van den Brule S; ''Mechanisms of lung fibrosis induced by carbon nanotubes: towards an Adverse Outcome Pathway (AOP).''; http://www.ncbi.nlm.nih.gov/pubmed/26926090, 2016 PubMed Europe PMC Scholia
  3. Montojo J, Zuberi K, Rodriguez H, Bader GD, Morris Q; ''GeneMANIA: Fast gene network construction and function prediction for Cytoscape.''; http://www.ncbi.nlm.nih.gov/pubmed/25254104, 2014 PubMed Europe PMC Scholia
  4. Davis AP, Grondin CJ, Lennon-Hopkins K, Saraceni-Richards C, Sciaky D2, King BL, Wiegers TC2, Mattingly CJ; ''The Comparative Toxicogenomics Database's 10th year anniversary: update 2015''; http://www.ncbi.nlm.nih.gov/pubmed/25326323, 2015 PubMed Europe PMC Scholia
  5. Naumanen P, Lappalainen P, Hotulainen P; ''Mechanisms of actin stress fibre assembly''; J Microsc. 2008 Sep;231(3):446-54. doi: 10.1111/j.1365-2818.2008.02057.x., 2008 PubMed Europe PMC Scholia
  6. Muir H.; ''The chondrocyte, architect of cartilage. Biomechanics, structure, function and molecular biology of cartilage matrix macromolecules.''; Bioessays. 1995 Dec;17(12):1039-48., 1995 PubMed Europe PMC Scholia
  7. Nymark P, Rieswijk L, Ehrhart F, Jeliazkova N, Tsiliki G, Sarimveis H, Evelo CT, Hongisto V, Kohonen P, Willighagen E, Grafström RC; ''A data fusion pipeline for generating and enriching Adverse Outcome Pathway descriptions.''; Toxicol Sci, 2017 PubMed Europe PMC Scholia
  8. Labib S, Williams A, Yauk CL, Nikota JK, Wallin H, Vogel U, Halappanavar S; ''Nano-risk Science: application of toxicogenomics in an adverse outcome pathway framework for risk assessment of multi-walled carbon nanotubes''; http://www.ncbi.nlm.nih.gov/pubmed/26979667, 2016 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
122572view10:54, 16 April 2022EgonwMade multiple pathways clickable
118417view14:20, 27 May 2021Mkutmonpublication ref fix
110182view14:31, 23 April 2020EgonwOntology Term : 'carbon nanotube response pathway' added !
109958view07:05, 8 April 2020PennyUpdated the Legend of the AOP description in line with the current AOP:173
106633view20:59, 12 September 2019KhanspersModified description
105638view05:06, 10 August 2019KhanspersModified description
102001view15:23, 23 November 2018EgonwRemove duplicate BioPax content.
95209view13:13, 23 November 2017PennyAdded reference to publication doi: 10.1093/toxsci/kfx252
94992view14:26, 24 October 2017Fehrhartfixed a label (MIE)
92327view12:06, 23 May 2017PennyUpdated links - SERPINA1 to Chemokine signaling; TGFA to SMAD7
91475view12:07, 6 March 2017FehrhartAdded ID for Chemokine signaling
91457view12:32, 1 March 2017FehrhartDesign update
91456view11:57, 1 March 2017FehrhartFormat adjustments
91455view10:13, 1 March 2017FehrhartAdded AE3
91421view12:48, 22 February 2017FehrhartChanged shade of grey for AO
90900view11:37, 16 December 2016PennyRemoved "frustrated phagocytosis" since that is mainly related to high-aspect ratio materials and does not represent other types of fibrosis-inducing agents
90691view13:12, 9 December 2016PennyModified description
90684view11:24, 7 December 2016PennyLink to WP2666
90683view11:13, 7 December 2016PennyAdded link to WP474
90526view23:51, 21 November 2016Khanspersmoved pathway to improve scaling/readability
88994view12:05, 18 August 2016LindarieswijkConverted unknown node to label
88993view11:54, 18 August 2016LindarieswijkUpdate literature reference (double Vietti)
88992view11:51, 18 August 2016LindarieswijkUpdates references
88991view11:50, 18 August 2016LindarieswijkUpdates literature
88990view11:47, 18 August 2016LindarieswijkUpdates literature reference
88984view10:00, 18 August 2016LindarieswijkUpdated legend and coloring of the events
88974view08:57, 18 August 2016LindarieswijkChanged "ROS production" labels to metabolite nodes and added CHEBI ID
88972view07:59, 18 August 2016LindarieswijkUpdated literature
88923view15:24, 17 August 2016LindarieswijkChanged AE back to associative event (like in paper)
88922view15:19, 17 August 2016LindarieswijkCorrected the legend: added MIE and adjusted full name AE
88695view16:04, 12 August 2016JmeliusOntology Term : 'respiratory system disease pathway' added !
87393view11:05, 22 July 2016MaintBotadded missing graphids
86044view19:07, 28 June 2016MaintBotconnected interaction
85998view00:08, 24 June 2016KhanspersModified description
85992view08:34, 23 June 2016FehrhartConnected unconnected lines
85985view19:02, 22 June 2016KhanspersOntology Term : 'pulmonary fibrosis' added !
85070view10:30, 11 April 2016PennyAdded legend for AOP events
84887view14:15, 30 March 2016PennyPeriodical update, work in progress
84886view13:47, 30 March 2016PennyPeriodical update, work in progress
84881view20:33, 29 March 2016PennyPeriodical update, work in progress
84880view20:03, 29 March 2016PennyPeriodical update
84877view15:34, 29 March 2016PennySimplified connections with reference to MIEs, KEs and AEs associated with a putative AOP for lung fibrosis.
84873view11:29, 29 March 2016FehrhartAdded link to NDRP3 inflammasome pathway via IL1B
84792view12:33, 22 March 2016PennyUpdated links
84791view10:33, 22 March 2016PennyUpdated connections according to geneMANIA and CPDB induced network module.
84790view09:07, 22 March 2016PennyUpdated connections
84789view08:36, 22 March 2016PennyAdded gene connections
84787view15:28, 21 March 2016LindarieswijkUpdated Gene IDs
84775view14:33, 18 March 2016Penny
84774view14:13, 18 March 2016Penny

External references

DataNodes

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NameTypeDatabase referenceComment
ATP11AGeneProductENSG00000068650 (Ensembl)
ApoptosisPathwayWP254 (WikiPathways)
BMP7GeneProductENSG00000101144 (Ensembl)
CALCAGeneProductENSG00000110680 (Ensembl)
CCL11GeneProductENSG00000172156 (Ensembl)
CCL2GeneProductENSG00000108691 (Ensembl)
CCL3GeneProductENSG00000277632 (Ensembl)
CCL4GeneProductENSG00000275302 (Ensembl)
CCL5GeneProductENSG00000271503 (Ensembl)
CCR2GeneProductENSG00000121807 (Ensembl)
CCR3GeneProductENSG00000183625 (Ensembl)
CEBPBGeneProductENSG00000172216 (Ensembl)
CMA1GeneProductENSG00000092009 (Ensembl)
CSF2GeneProductENSG00000164400 (Ensembl)
CSF3GeneProductENSG00000108342 (Ensembl)
CTGFGeneProductENSG00000118523 (Ensembl)
CXCL2GeneProductENSG00000081041 (Ensembl)
CXCL8GeneProductENSG00000169429 (Ensembl)
CYSLTR2GeneProductENSG00000152207 (Ensembl)
Chemokine signalingPathwayWP3929 (WikiPathways)
Chondrocyte differentiationPathwayWP474 (WikiPathways) Link to the pathway Endochondrial ossification describing chondrocyte differentiation. Chondrocytes produce and maintain cartilage consisting mainly of collagen and proteoglycans.
Coagulation disturbancesPathwayWP558 (WikiPathways)
Collagen productonPathwayWP2798 (WikiPathways)
Cytokines

and inflammatory

response		PathwayWP530 (WikiPathways)
DPP9GeneProductENSG00000142002 (Ensembl)
DSPGeneProductENSG00000096696 (Ensembl)
Differentiation PathwayPathwayWP2848 (WikiPathways)
EDN1GeneProductENSG00000078401 (Ensembl)
EGFGeneProductENSG00000138798 (Ensembl)
ELMOD2GeneProductENSG00000179387 (Ensembl)
ELNGeneProductENSG00000049540 (Ensembl)
FAM13AGeneProductENSG00000138640 (Ensembl)
FGF1GeneProductENSG00000113578 (Ensembl)
FGF2GeneProductENSG00000138685 (Ensembl)
FGF7GeneProductENSG00000140285 (Ensembl)
GREM1GeneProductENSG00000166923 (Ensembl)
HGFGeneProductENSG00000019991 (Ensembl)
HMOX1GeneProductENSG00000100292 (Ensembl)
IGF1GeneProductENSG00000017427 (Ensembl)
IL12BGeneProductENSG00000113302 (Ensembl)
IL13GeneProductENSG00000169194 (Ensembl)
IL1BGeneProductENSG00000125538 (Ensembl)
IL4GeneProductENSG00000113520 (Ensembl)
IL5GeneProductENSG00000113525 (Ensembl)
IL6GeneProductENSG00000136244 (Ensembl)
Inflammasome activationPathwayWP288 (WikiPathways)
InflammationPathwayWP453 (WikiPathways)
MAPK signalingPathwayWP382 (WikiPathways)
MECP2GeneProductENSG00000169057 (Ensembl)
MMP2GeneProductENSG00000087245 (Ensembl)
MMP9GeneProductENSG00000100985 (Ensembl)
MT2AGeneProductENSG00000125148 (Ensembl)
MUC5BGeneProductENSG00000117983 (Ensembl)
Matrix metalloproteinasesPathwayWP129 (WikiPathways)
NADPH oxidasePathwayWP3396 (WikiPathways)
NF-KBPathwayhsa04064 (KEGG Pathway)
NFE2L2GeneProductENSG00000116044 (Ensembl)
NRF2 signalingPathwayWP2884 (WikiPathways)
OBFC1GeneProductENSG00000107960 (Ensembl)
Oxidative StressPathwayWP408 (WikiPathways)
PARNGeneProductENSG00000140694 (Ensembl)
PDGFAGeneProductENSG00000197461 (Ensembl)
PDGFBGeneProductENSG00000100311 (Ensembl)
PLAUGeneProductENSG00000122861 (Ensembl)
PTX3GeneProductENSG00000163661 (Ensembl)
ROS productionMetaboliteCHEBI:26523 (ChEBI)
RTEL1GeneProductENSG00000258366 (Ensembl)
SERPINA1GeneProductENSG00000197249 (Ensembl)
SFTPA1GeneProductENSG00000122852 (Ensembl)
SFTPA2GeneProductENSG00000185303 (Ensembl)
SFTPCGeneProductENSG00000168484 (Ensembl)
SKILGeneProductENSG00000136603 (Ensembl)
SMAD7GeneProductENSG00000101665 (Ensembl)
SPP1GeneProductENSG00000118785 (Ensembl)
Stress fibre assemblyPathwayWP2666 (WikiPathways) Link to Elastic fibre formation, which describes the dynamic connective tissues such as large arteries and lung parenchyma. The stress fibre assembly related gene ELN is involved in this pathway.
TERCGeneProductENSG00000270141 (Ensembl)
TERTGeneProductENSG00000164362 (Ensembl)
TGF beta signalingPathwayWP560 (WikiPathways)
TGFAGeneProductENSG00000163235 (Ensembl)
TGFB1GeneProductENSG00000105329 (Ensembl)
TIMP1GeneProductENSG00000102265 (Ensembl)
TNFGeneProductENSG00000232810 (Ensembl)
Toll-like receptor signalingPathwayWP75 (WikiPathways)
p38 MAPKPathwayWP400 (WikiPathways)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP3624"
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