Lung fibrosis (Mus musculus)

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7MIE - Molecular Initiating EventDifferentiationPathwayCytokinesand inflammatoryresponseApoptosisMatrixmetalloproteinasesTGF betasignalingNRF2signalingToll-like receptorsignaling32GPCRsignalingRegulation ofreactive oxygen speciesmetabolismGTPaseactivatorChemokinesignalingPulmonary fibrosisFibroblastproliferation, resistance to apoptosis, differentiationinto myofibroblasts, collagen productionPulmonary surfactantproteinsMacrophage-relatedfrustrated phagocytosis, oxidative stressandinflammasome activationMIESalivarysecretion4Epithelial 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)2Rtel1Cxcl2 Spp1Dpp9Fgf1Ccl4Smad7 TercCtgfSFTPA2ParnMAPKsignalingCcl2 SERPINA1Skil TnfSftpa1Il6Oxidative StressEdn1ElnCsf3 Grem1Inflammasomeactivation5DspTertMecp2Cxcl15Obfc1CalcaTgfaIl13Il1bCcr3 Ccl5Pdgfa NADPHoxidaseCcl11Atp11aFgf2InflammationCma1Il5Coagulation disturbancesEgf Timp1 NF-KBIl12bBmp7Pdgfb Ptx3Nfe2l2Mmp9Fgf7Muc5bCebpbCysltr2Hmox1 p38 MAPKMmp2 HgfSftpcCcr2Il4Csf2 Elmod2PlauFam13aCcl3Mt2Igf1 Tgfb1ROSproduction5Additional non-connected genes with direct association topulmonary fibrosis in the Comparative Toxicogenomics Database (CTD)6All genes in the network are directly associated withpulmonary fibrosis in the Comparative Toxicogenomics Database (CTD)ROSproduction6, 85NF-KBInflammasomeactivationKE15KE1/KE344KE1/KE34KE1/KE2KE3/KE444KE34KE3/KE44KE3KE44KE444AO4KE1/KE24AE1AE14AE144AE24AE1KE3/KE44KE3/KE444KE34KE1 - Induction of inflammatory cytokines and acute phase responseKE5 - Excessive ECM depositionAE - Associative Event KE3 - TH2/M2 response, secretion/activation of interleukins and growth factorsMIE - Cellular sensing of substanceAE1 - Increase of reactive oxygen species levelsAE2 - Cellular toxicity, cell deathKE2 - a. Retention/repeated exposure, b. persistent inflammationAO - FibrosisKE4 - Fibroblast & myofibroblast proliferationKE - Key EventAO - Adverse OutcomeEvents related to a putative Adverse Outcome Pathway forpulmonary fibrosis4LegendAE3 - Collagen productionChondrocytedifferentiation9Stressfibre assembly1Excess deposition and/or reduced turnover of extracellular matrix (ECM)KE54Collagen productonAE3


(Nanoparticle) induced lung fibrosis pathway. Note! Mouse homologues for SERPINA1 and SFTPA2 are missing and the pathway currently contains the human equivalents. Other users are encouraged to add this information when available.

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  1. 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
  2. Todd NW, Luzina IG, Atamas SP; ''Molecular and cellular mechanisms of pulmonary fibrosis.'';, 2012 PubMed Europe PMC Scholia
  3. Todd NW, Luzina IG, Atamas SP; ''Molecular and cellular mechanisms of pulmonary fibrosis.'';, 2012 PubMed Europe PMC Scholia
  4. 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'';, 2016 PubMed Europe PMC Scholia
  5. Vietti G, Lison D, van den Brule S; ''Mechanisms of lung fibrosis induced by carbon nanotubes: towards an Adverse Outcome Pathway (AOP).''; , 2016 PubMed Europe PMC Scholia
  6. 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'';, 2015 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. Montojo J, Zuberi K, Rodriguez H, Bader GD, Morris Q; ''GeneMANIA: Fast gene network construction and function prediction for Cytoscape.'';, 2014 PubMed Europe PMC Scholia
  9. 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
  10. Vietti G, Lison D, van den Brule S; ''Mechanisms of lung fibrosis induced by carbon nanotubes: towards an Adverse Outcome Pathway (AOP).'';, 2016 PubMed Europe PMC Scholia
  11. Grebe A, Latz E; ''Cholesterol crystals and inflammation.''; Curr Rheumatol Rep, 2013 PubMed Europe PMC Scholia


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114011view14:53, 17 December 2020LaurentConnected line
111191view07:14, 23 July 2020EgonwMade a new more pathway nodes clickable
104818view12:47, 19 June 2019FehrhartModified description
102002view15:27, 23 November 2018EgonwRemoved whitespace in PubMed identifiers and duplicate BioPax content.
95210view13:14, 23 November 2017PennyAdded reference to publication doi: 10.1093/toxsci/kfx252
94993view15:03, 24 October 2017Fehrhartfixed a label (MIE)
92326view12:05, 23 May 2017PennyUpdated links - SERPINA1 to Chemokine signaling; TGFA to SMAD7
92001view11:17, 13 April 2017FehrhartUpdate linked human/mouse pathways
92000view11:12, 13 April 2017FehrhartUpdate of linked mouse pathways
91992view09:29, 13 April 2017FehrhartUpdated graphics to match human lung fibrosis pathway
88699view16:06, 12 August 2016JmeliusOntology Term : 'respiratory system disease pathway' added !
88697view16:05, 12 August 2016JmeliusOntology Term : 'pulmonary fibrosis' added !
88696view16:04, 12 August 2016JmeliusOntology Term : 'DOID:3770' removed !
88168view08:44, 29 July 2016Mkutmonunconnected line
87400view11:05, 22 July 2016MaintBotadded missing graphids
86204view08:42, 6 July 2016PennyModified description
86171view10:13, 5 July 2016FehrhartAdded homologues for some (human) gene products
86045view19:14, 28 June 2016MaintBotconnected interactions
85986view19:06, 22 June 2016KhanspersOntology Term : 'pulmonary fibrosis' added !
85025view09:47, 6 April 2016FehrhartNew pathway

External references


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NameTypeDatabase referenceComment
ApoptosisPathwayWP1254 (WikiPathways)
Atp11aGeneProductENSMUSG00000031441 (Ensembl)
Bmp7GeneProductENSMUSG00000008999 (Ensembl)
CalcaGeneProductENSMUSG00000030669 (Ensembl)
Ccl11GeneProductENSMUSG00000020676 (Ensembl)
Ccl2 GeneProductENSMUSG00000035385 (Ensembl)
Ccl3GeneProductENSMUSG00000000982 (Ensembl)
Ccl4GeneProductENSMUSG00000018930 (Ensembl)
Ccl5GeneProductENSMUSG00000035042 (Ensembl)
Ccr2GeneProductENSMUSG00000049103 (Ensembl)
Ccr3 GeneProductENSMUSG00000035448 (Ensembl)
CebpbGeneProductENSMUSG00000056501 (Ensembl)
Chondrocyte differentiationPathwayWP1270 (WikiPathways) Link to the pathway Endochondrial ossification describing chondrocyte differentiation. Chondrocytes produce and maintain cartilage consisting mainly of collagen and proteoglycans.
Cma1GeneProductENSMUSG00000022225 (Ensembl)
Coagulation disturbancesPathwayWP449 (WikiPathways)
Collagen productonPathwayWP2798 (WikiPathways) Human pathway - mouse not available yet
Csf2 GeneProductENSMUSG00000018916 (Ensembl)
Csf3 GeneProductENSMUSG00000038067 (Ensembl)
CtgfGeneProductENSMUSG00000019997 (Ensembl)
Cxcl15GeneProductENSMUSG00000029375 (Ensembl)
Cxcl2 GeneProductENSMUSG00000058427 (Ensembl)
Cysltr2GeneProductENSMUSG00000033470 (Ensembl)

and inflammatory

PathwayWP222 (WikiPathways)
Differentiation PathwayPathwayWP2848 (WikiPathways) Human pathway - mouse not yet available
Dpp9GeneProductENSMUSG00000001229 (Ensembl)
DspGeneProductENSMUSG00000054889 (Ensembl)
Edn1GeneProductENSMUSG00000021367 (Ensembl)
Egf GeneProductENSMUSG00000028017 (Ensembl)
Elmod2GeneProductENSMUSG00000035151 (Ensembl)
ElnGeneProductENSMUSG00000029675 (Ensembl)
Fam13aGeneProductENSMUSG00000037709 (Ensembl)
Fgf1 GeneProductENSMUSG00000036585 (Ensembl)
Fgf2GeneProductENSMUSG00000037225 (Ensembl)
Fgf7GeneProductENSMUSG00000027208 (Ensembl)
Grem1GeneProductENSMUSG00000074934 (Ensembl)
HgfGeneProductENSMUSG00000028864 (Ensembl)
Hmox1 GeneProductENSMUSG00000005413 (Ensembl)
Igf1 GeneProductENSMUSG00000020053 (Ensembl)
Il12bGeneProductENSMUSG00000004296 (Ensembl)
Il13GeneProductENSMUSG00000020383 (Ensembl)
Il1bGeneProductENSMUSG00000027398 (Ensembl)
Il4GeneProductENSMUSG00000000869 (Ensembl)
Il5GeneProductENSMUSG00000036117 (Ensembl)
Il6GeneProductENSMUSG00000025746 (Ensembl)
Inflammasome activationPathwayWP1256 (WikiPathways)
InflammationPathwayWP458 (WikiPathways)
MAPK signalingPathwayWP493 (WikiPathways)
Matrix metalloproteinasesPathwayWP441 (WikiPathways)
Mecp2GeneProductENSMUSG00000031393 (Ensembl)
Mmp2 GeneProductENSMUSG00000031740 (Ensembl)
Mmp9GeneProductENSMUSG00000017737 (Ensembl)
Mt2GeneProductENSMUSG00000031762 (Ensembl)
Muc5bGeneProductENSMUSG00000066108 (Ensembl)
NADPH oxidasePathwayWP3396 (WikiPathways) Human pathway - mouse pathway not yet available
NF-KBPathwaymmu04064 (KEGG Pathway)
NRF2 signalingPathwayWP2884 (WikiPathways) Human pathway - mouse not yet available
Nfe2l2GeneProductENSMUSG00000015839 (Ensembl)
Obfc1GeneProductENSMUSG00000042694 (Ensembl)
Oxidative StressPathwayWP412 (WikiPathways)
ParnGeneProductENSMUSG00000022685 (Ensembl)
Pdgfa GeneProductENSMUSG00000025856 (Ensembl)
Pdgfb GeneProductENSMUSG00000000489 (Ensembl)
PlauGeneProductENSMUSG00000021822 (Ensembl)
Ptx3GeneProductENSMUSG00000027832 (Ensembl)
Rtel1GeneProductENSMUSG00000038685 (Ensembl)
SERPINA1GeneProductENSG00000197249 (Ensembl) Human gene product - no annotation for mouse yet
SFTPA2GeneProductENSG00000185303 (Ensembl) Human gene product - no annotation for mouse yet
Sftpa1GeneProductENSMUSG00000021789 (Ensembl)
SftpcGeneProductENSMUSG00000022097 (Ensembl)
Skil GeneProductENSMUSG00000027660 (Ensembl)
Smad7 GeneProductENSMUSG00000025880 (Ensembl)
Spp1GeneProductENSMUSG00000029304 (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.
  • Human pathway, mouse is not yet available
TGF beta signalingPathwayWP258 (WikiPathways)
TercGeneProductENSMUSG00000064796 (Ensembl)
TertGeneProductENSMUSG00000021611 (Ensembl)
TgfaGeneProductENSMUSG00000029999 (Ensembl)
Tgfb1GeneProductENSMUSG00000002603 (Ensembl)
Timp1 GeneProductENSMUSG00000001131 (Ensembl)
TnfGeneProductENSMUSG00000024401 (Ensembl)
Toll-like receptor signalingPathwayWP1271 (WikiPathways)
p38 MAPKPathwayWP350 (WikiPathways)

Annotated Interactions

No annotated interactions

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