Lung fibrosis (Mus musculus)

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MIE - Molecular Initiating Event Cytokines and inflammatory response TGF beta signaling NRF2 signaling Toll-like receptor signaling Matrix metalloproteinases Differentiation Pathway Apoptosis Eln GPCR signaling Regulation of reactive oxygen species metabolism GTPase activator Chemokine signaling Pulmonary fibrosis AO Fibroblast proliferation, resistance to apoptosis, differentiation into myofibroblasts, collagen production Pulmonary surfactant proteins SFTPA2 Sftpa1 Sftpc Macrophage-related frustrated phagocytosis, oxidative stress and inflammasome activation MIE Salivary secretion Epithelial injury and apoptosis: disturbed interaction with mesenchymal cells, epithelial-mesenchymal transition Telomere organization Serine-type peptidase activity Dpp9 Leukocyte/Myeloid cell differentiation Calca Cebpb KE3 Intermediate filament cytoskeleton Methylation/ chromatin binding Lung injury (known or unknown) combined with tissue response (normal or abnormal) Rtel1 Cxcl2 Il6 Csf3 Il13 Pdgfa Il5 Il12b Il4 Csf2 Spp1 Skil Fgf1 Fgf2 Egf Fgf7 Hgf Igf1 Ccl4 Cxcl15 Ccl5 Ccl3 Smad7 Terc Ctgf Tgfa Parn MAPK signaling KE4 Ccl2 SERPINA1 Nfe2l2 Hmox1 Tnf Oxidative Stress Edn1 Bmp7 Ptx3 Plau Grem1 Atp11a Inflammasome activation Dsp Obfc1 Tert Mecp2 Il1b KE1 Ccr3 Ccl11 Ccr2 NADPH oxidase Inflammation Cma1 Coagulation disturbances Timp1 Mmp9 Mmp2 NF-KB KE1/KE2 Pdgfb KE3/KE4 Muc5b Cysltr2 Fam13a p38 MAPK KE4 Elmod2 Mt2 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 KE1/KE3 KE1/KE3 KE3/KE4 KE3 AE1 AE2 AE1 KE3/KE4 KE3 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 AO - Fibrosis KE4 - Fibroblast & myofibroblast proliferation KE - Key Event AO - Adverse Outcome Events related to a putative Adverse Outcome Pathway for pulmonary fibrosis Legend AE3 - Collagen production Chondrocyte differentiation Stress fibre assembly Excess deposition and/or reduced turnover of extracellular matrix (ECM) KE5 Collagen producton AE3 Name: Lung fibrosis Organism: Mus musculus


(Nanoparticle) induced lung fibrosis pathway. Under construction. 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.

Quality Tags

Ontology Terms



  1. 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
  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. Grebe A, Latz E; ''Cholesterol crystals and inflammation.''; Curr Rheumatol Rep, 2013 PubMed
  4. Todd NW, Luzina IG, Atamas SP; ''Molecular and cellular mechanisms of pulmonary fibrosis.'';, 2012 PubMed
  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
  6. Todd NW, Luzina IG, Atamas SP; ''Molecular and cellular mechanisms of pulmonary fibrosis.'';, 2012 PubMed
  7. Montojo J, Zuberi K, Rodriguez H, Bader GD, Morris Q; ''GeneMANIA: Fast gene network construction and function prediction for Cytoscape.'';, 2014 PubMed
  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'';, 2016 PubMed
  9. Vietti G, Lison D, van den Brule S; ''Mechanisms of lung fibrosis induced by carbon nanotubes: towards an Adverse Outcome Pathway (AOP).''; , 2016 PubMed
  10. 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
  11. 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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95210view 06:14, 23 November 2017PennyAdded reference to publication doi: 10.1093/toxsci/kfx252
94993view 08:03, 24 October 2017Fehrhartfixed a label (MIE)
92326view 05:05, 23 May 2017PennyUpdated links - SERPINA1 to Chemokine signaling; TGFA to SMAD7
92001view 04:17, 13 April 2017FehrhartUpdate linked human/mouse pathways
92000view 04:12, 13 April 2017FehrhartUpdate of linked mouse pathways
91992view 02:29, 13 April 2017FehrhartUpdated graphics to match human lung fibrosis pathway
88699view 09:06, 12 August 2016JmeliusOntology Term : 'respiratory system disease pathway' added !
88697view 09:05, 12 August 2016JmeliusOntology Term : 'pulmonary fibrosis' added !
88696view 09:04, 12 August 2016JmeliusOntology Term : 'DOID:3770' removed !
88168view 01:44, 29 July 2016Mkutmonunconnected line
87400view 04:05, 22 July 2016MaintBotadded missing graphids
86204view 01:42, 6 July 2016PennyModified description
86171view 03:13, 5 July 2016FehrhartAdded homologues for some (human) gene products
86045view 12:14, 28 June 2016MaintBotconnected interactions
85986view 12:06, 22 June 2016KhanspersOntology Term : 'pulmonary fibrosis' added !
85025view 02:47, 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

<cite>No annotated interactions</cite>