Lung fibrosis (Homo sapiens)

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Collagen producton AE3 GTPase activator ELMOD2 Cytokines and inflammatory response CXCL2 IL6 CSF3 IL13 PDGFA IL5 IL12B IL4 CSF2 KE1/KE3 Differentiation Pathway FGF1 FGF2 EGF FGF7 HGF IGF1 KE3/KE4 GPCR signaling CYSLTR2 FAM13A Pulmonary surfactant proteins SFTPA2 SFTPA1 SFTPC TGF beta signaling SPP1 SKIL KE3 NRF2 signaling SERPINA1 NFE2L2 HMOX1 AE1 Apoptosis MIE CCL4 CCL2 CXCL8 CCR3 CCL5 CCL11 CCR2 CCL3 KE1/KE3 AE2 Toll-like receptor signaling Matrix metalloproteinases TIMP1 MMP9 MMP2 KE3 KE3/KE4 Pulmonary fibrosis AO Excess deposition and/or reduced turnover of extracellular matrix (ECM) KE5 KE1 - Induction of inflammatory cytokines and acute phase response KE5 - Excessive ECM deposition AE - Associative Event KE3 - TH2/M2 response, secretion/activation of interleukins and growth factors MIE - Cellular sensing of substance AE1 - Increase of reactive oxygen species levels AE2 - Cellular toxicity, cell death KE2 - a. Retention/repeated exposure, b. persistent inflammation MIE - Molecular Initiating Event AO - Fibrosis KE4 - Fibroblast & myofibroblast proliferation KE - Key Event AO - Adverse Outcome Chemokine signaling Chondrocyte differentiation Stress fibre assembly Methylation/ chromatin binding MECP2 Telomere organization RTEL1 TERC TERT ELN Serine-type peptidase activity DPP9 Regulation of reactive oxygen species metabolism EDN1 BMP7 PTX3 PLAU AE1 Leukocyte/Myeloid cell differentiation CALCA CEBPB KE3 Salivary secretion MUC5B Fibroblast proliferation, resistance to apoptosis, differentiation into myofibroblasts, collagen production Macrophage-related oxidative stress and inflammasome activation Epithelial injury and apoptosis: disturbed interaction with mesenchymal cells, epithelial-mesenchymal transition Intermediate filament cytoskeleton Lung injury (known or unknown) combined with tissue response (normal or abnormal) SMAD7 CTGF TGFA PARN MAPK signaling KE4 TNF Oxidative Stress Inflammation Coagulation disturbances GREM1 ATP11A Inflammasome activation DSP OBFC1 IL1B KE1 NADPH oxidase CMA1 NF-KB KE1/KE2 PDGFB KE3/KE4 p38 MAPK KE4 MT2A TGFB1 KE3/KE4 ROS production AE1 Additional non-connected genes with direct association to pulmonary fibrosis in the Comparative Toxicogenomics Database (CTD) All genes in the network are directly associated with pulmonary fibrosis in the Comparative Toxicogenomics Database (CTD) ROS production AE1 NF-KB KE1/KE2 Inflammasome activation Events related to a putative Adverse Outcome Pathway for pulmonary fibrosis Legend AE3 - Collagen production Name: Lung fibrosis Organism: Homo sapiens


Description

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

Quality Tags

Ontology Terms

<OntologyTags></OntologyTags>

Bibliography

  1. Todd NW, Luzina IG, Atamas SP; ''Molecular and cellular mechanisms of pulmonary fibrosis.''; http://www.ncbi.nlm.nih.gov/pubmed/22824096, 2012 PubMed
  2. 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
  3. 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
  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
  5. 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
  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
  7. Grebe A, Latz E; ''Cholesterol crystals and inflammation.''; Curr Rheumatol Rep, 2013 PubMed
  8. 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
  9. 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
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History

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RevisionActionTimeUserComment
95209view 06:13, 23 November 2017PennyAdded reference to publication doi: 10.1093/toxsci/kfx252
94992view 07:26, 24 October 2017Fehrhartfixed a label (MIE)
92327view 05:06, 23 May 2017PennyUpdated links - SERPINA1 to Chemokine signaling; TGFA to SMAD7
91475view 05:07, 6 March 2017FehrhartAdded ID for Chemokine signaling
91457view 05:32, 1 March 2017FehrhartDesign update
91456view 04:57, 1 March 2017FehrhartFormat adjustments
91455view 03:13, 1 March 2017FehrhartAdded AE3
91421view 05:48, 22 February 2017FehrhartChanged shade of grey for AO
90900view 04:37, 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
90691view 06:12, 9 December 2016PennyModified description
90684view 04:24, 7 December 2016PennyLink to WP2666
90683view 04:13, 7 December 2016PennyAdded link to WP474
90526view 16:51, 21 November 2016Khanspersmoved pathway to improve scaling/readability
88994view 05:05, 18 August 2016LindarieswijkConverted unknown node to label
88993view 04:54, 18 August 2016LindarieswijkUpdate literature reference (double Vietti)
88992view 04:51, 18 August 2016LindarieswijkUpdates references
88991view 04:50, 18 August 2016LindarieswijkUpdates literature
88990view 04:47, 18 August 2016LindarieswijkUpdates literature reference
88984view 03:00, 18 August 2016LindarieswijkUpdated legend and coloring of the events
88974view 01:57, 18 August 2016LindarieswijkChanged "ROS production" labels to metabolite nodes and added CHEBI ID
88972view 00:59, 18 August 2016LindarieswijkUpdated literature
88923view 08:24, 17 August 2016LindarieswijkChanged AE back to associative event (like in paper)
88922view 08:19, 17 August 2016LindarieswijkCorrected the legend: added MIE and adjusted full name AE
88695view 09:04, 12 August 2016JmeliusOntology Term : 'respiratory system disease pathway' added !
87393view 04:05, 22 July 2016MaintBotadded missing graphids
86044view 12:07, 28 June 2016MaintBotconnected interaction
85998view 17:08, 23 June 2016KhanspersModified description
85992view 01:34, 23 June 2016FehrhartConnected unconnected lines
85985view 12:02, 22 June 2016KhanspersOntology Term : 'pulmonary fibrosis' added !
85070view 03:30, 11 April 2016PennyAdded legend for AOP events
84887view 07:15, 30 March 2016PennyPeriodical update, work in progress
84886view 06:47, 30 March 2016PennyPeriodical update, work in progress
84881view 13:33, 29 March 2016PennyPeriodical update, work in progress
84880view 13:03, 29 March 2016PennyPeriodical update
84877view 08:34, 29 March 2016PennySimplified connections with reference to MIEs, KEs and AEs associated with a putative AOP for lung fibrosis.
84873view 04:29, 29 March 2016FehrhartAdded link to NDRP3 inflammasome pathway via IL1B
84792view 05:33, 22 March 2016PennyUpdated links
84791view 03:33, 22 March 2016PennyUpdated connections according to geneMANIA and CPDB induced network module.
84790view 02:07, 22 March 2016PennyUpdated connections
84789view 01:36, 22 March 2016PennyAdded gene connections
84787view 08:28, 21 March 2016LindarieswijkUpdated Gene IDs
84775view 07:33, 18 March 2016Penny
84774view 07:13, 18 March 2016Penny
84773view 07:06, 18 March 2016Penny
84772view 05:38, 18 March 2016FehrhartModified description
84771view 05:30, 18 March 2016FehrhartNew pathway

External references

DataNodes

View all...
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

<cite>No annotated interactions</cite>