SOMA mechanisms KB

Key-event network

Key events and their relationships pooled across all 40 extracted papers, in the style of an adverse-outcome pathway: columns go from molecular initiating events on the left to organism-level outcomes on the right. Click a node to jump to its evidence; line style shows the strength of support recorded for each relationship.

molecular cellular tissue organ organism strong moderate weak / not specified
molecularcellulartissueorganorganismIncreased oxidative stress directly leads to Mucus secretory program activation (moderate support)Increased oxidative stress directly leads to Club cell marker loss (moderate support)Increased oxidative stress directly leads to / indirectly leads to Airway inflammation (strong support)Airway inflammation directly leads to / indirectly leads to Altered epithelial barrier integrity (strong support)Decreased ciliary function directly leads to Impaired mucociliary clearance (moderate support)Increased oxidative stress associated with / indirectly leads to Decreased lung function (moderate support)Increased oxidative stress directly leads to Increased DNA damage (moderate support)Increased oxidative stress directly leads to EGFR activation (moderate support)AhR pathway activation directly leads to EGFR activation (moderate support)EGFR activation directly leads to Increased cell proliferation (moderate support)IL-1 inflammatory program activation directly leads to Airway inflammation (moderate support)IL-1 inflammatory program activation indirectly leads to Lung cancer (weak support)Increased DNA damage directly leads to Lung cancer (moderate support)Increased cell proliferation directly leads to Lung cancer (weak support)Airway inflammation indirectly leads to Lung cancer (moderate support)TRP channel activation directly leads to Airway inflammation (moderate support)TLR4 activation directly leads to Airway inflammation (moderate support)AhR pathway activation directly leads to Inhibited apoptosis (moderate support)EGFR activation directly leads to Inhibited apoptosis (weak support)Inhibited apoptosis indirectly leads to Airway inflammation (weak support)Inhibited apoptosis indirectly leads to Airway remodeling (weak support)PI3K/AKT pathway activation indirectly leads to Suppressed apoptosis (moderate support)PI3K/AKT pathway activation indirectly leads to Increased cell proliferation (moderate support)PI3K/AKT pathway activation indirectly leads to Increased pro-angiogenic signaling (moderate support)EGFR activation directly leads to PI3K/AKT pathway activation (weak support)Disturbed epithelial signal transduction and renewal indirectly leads to Airway remodeling (weak support)PI3K/AKT/mTOR signaling activation directly leads to Increased autophagy (strong support)Increased autophagy directly leads to Increased epithelial cell apoptosis (moderate support)Increased epithelial cell apoptosis indirectly leads to Decreased lung function (moderate support)Increased oxidative stress indirectly leads to Increased epithelial cell apoptosis (weak support)EGFR activation indirectly leads to Airway inflammation (weak support)AhR pathway activation indirectly leads to Airway inflammation (moderate support)Airway inflammation associated with Increased systemic inflammation (weak support)Airway inflammation indirectly leads to Goblet cell hyperplasia (moderate support)Goblet cell hyperplasia directly leads to Mucin hypersecretion (moderate support)Mucin hypersecretion associated with / indirectly leads to Decreased lung function (moderate support)Airway inflammation directly leads to / indirectly leads to Decreased lung function (moderate support)EGFR activation directly leads to Mucin hypersecretion (strong support)EGFR activation directly leads to Goblet cell hyperplasia (moderate support)Increased oxidative stress directly leads to ERK1/2 activation (strong support)ERK1/2 activation directly leads to Altered epithelial barrier integrity (strong support)Altered epithelial barrier integrity directly leads to Mucin hypersecretion (strong support)Decreased CFTR function directly leads to Decreased ASL height (moderate support)Increased oxidative stress indirectly leads to Increased cell proliferation (moderate support)Increased miR-155 expression directly leads to Decreased FOXO3a expression (strong support)Decreased FOXO3a expression directly leads to Increased oxidative stress (strong support)Mucin hypersecretion directly leads to Decreased ciliary beat frequency (weak support)Decreased Muc5b expression indirectly leads to Impaired mucociliary clearance (weak support)Goblet cell hyperplasia directly leads to Impaired mucociliary clearance (moderate support)Airway inflammation indirectly leads to Mucin hypersecretion (moderate support)Goblet cell hyperplasia directly leads to Club cell marker loss (moderate support)Altered ciliogenesis directly leads to Decreased ciliary function (moderate support)Decreased ciliary beat frequency directly leads to Impaired mucociliary clearance (moderate support)Decreased ASL height directly leads to Impaired mucociliary clearance (moderate support)Impaired mucociliary clearance indirectly leads to Airway inflammation (weak support)Increased oxidative stress directly leads to PI3K/AKT pathway activation (moderate support)PI3K/AKT pathway activation directly leads to Airway inflammation (moderate support)Decreased P2Y2R expression directly leads to Decreased intracellular calcium (moderate support)Decreased intracellular calcium indirectly leads to Decreased CFTR function (weak support)Decreased P2Y2R expression directly leads to Decreased CFTR function (moderate support)Decreased CFTR function indirectly leads to Airway inflammation (moderate support)EGFR activation directly leads to Altered ciliogenesis (moderate support)EGFR activation directly leads to Basal cell hyperplasia (moderate support)EGFR activation directly leads to Alveolar epithelial type II cell hyperplasia (moderate support)EGFR activation indirectly leads to Mucus secretory program activation (weak support)EGFR activation indirectly leads to Impaired alveolar epithelial type I cell differentiation (weak support)AhR pathway activation directly leads to IL-1 inflammatory program activation (moderate support)IL-1 inflammatory program activation directly leads to Goblet cell hyperplasia (moderate support)Decreased CFTR function directly leads to Impaired mucociliary clearance (weak support)Increased oxidative stress associated with Increased systemic inflammation (weak support)Altered ciliogenesis indirectly leads to Impaired mucociliary clearance (weak support)AhR pathway activation (molecular; 6 paper(s))AhR pathway activationDecreased CFTR function (molecular; 3 paper(s))Decreased CFTR functionDecreased FOXO3a expression (molecular; 1 paper(s))Decreased FOXO3a expressionDecreased intracellular calcium (molecular; 1 paper(s))Decreased intracellularcalciumDecreased P2Y2R expression (molecular; 1 paper(s))Decreased P2Y2R expressionEGFR activation (molecular; 10 paper(s))EGFR activationERK1/2 activation (molecular; 1 paper(s))ERK1/2 activationIL-1 inflammatory program activation (molecular; 2 paper(s))IL-1 inflammatory programactivationIncreased DNA damage (molecular; 1 paper(s))Increased DNA damageIncreased miR-155 expression (molecular; 1 paper(s))Increased miR-155 expressionIncreased oxidative stress (molecular; 17 paper(s))Increased oxidative stressPI3K/AKT pathway activation (molecular; 2 paper(s))PI3K/AKT pathway activationPI3K/AKT/mTOR signaling activation (molecular; 1 paper(s))PI3K/AKT/mTOR signalingactivationTLR4 activation (molecular; 1 paper(s))TLR4 activationTRP channel activation (molecular; 1 paper(s))TRP channel activationAltered ciliogenesis (cellular; 5 paper(s))Altered ciliogenesisAltered epithelial barrier integrity (cellular; 3 paper(s))Altered epithelial barrierintegrityAlveolar epithelial type II cell hyperplasia (cellular; 1 paper(s))Alveolar epithelial type IIcell hyperplasiaBasal cell hyperplasia (cellular; 1 paper(s))Basal cell hyperplasiaClub cell marker loss (cellular; 4 paper(s))Club cell marker lossDecreased ASL height (cellular; 3 paper(s))Decreased ASL heightDecreased ciliary beat frequency (cellular; 3 paper(s))Decreased ciliary beatfrequencyDecreased ciliary function (cellular; 4 paper(s))Decreased ciliary functionDecreased MUC5AC expression (cellular; 1 paper(s))Decreased MUC5AC expressionDecreased Muc5b expression (cellular; 1 paper(s))Decreased Muc5b expressionDisturbed epithelial signal transduction and renewal (cellular; 1 paper(s))Disturbed epithelial signaltransduction and renewalGoblet cell hyperplasia (cellular; 11 paper(s))Goblet cell hyperplasiaImpaired alveolar epithelial type I cell differentiation (cellular; 1 paper(s))Impaired alveolar epithelialtype I cell differentiationIncreased autophagy (cellular; 1 paper(s))Increased autophagyIncreased cell proliferation (cellular; 4 paper(s))Increased cell proliferationIncreased epithelial cell apoptosis (cellular; 1 paper(s))Increased epithelial cellapoptosisIncreased pro-angiogenic signaling (cellular; 1 paper(s))Increased pro-angiogenicsignalingInhibited apoptosis (cellular; 1 paper(s))Inhibited apoptosisMucin hypersecretion (cellular; 11 paper(s))Mucin hypersecretionMucus secretory program activation (cellular; 3 paper(s))Mucus secretory programactivationSuppressed apoptosis (cellular; 1 paper(s))Suppressed apoptosisAirway inflammation (tissue; 16 paper(s))Airway inflammationAirway remodeling (tissue; 2 paper(s))Airway remodelingImpaired mucociliary clearance (tissue; 7 paper(s))Impaired mucociliaryclearanceSquamous metaplasia (tissue; 1 paper(s))Squamous metaplasiaDecreased lung function (organ; 21 paper(s))Decreased lung functionIncreased systemic inflammation (organism; 5 paper(s))Increased systemicinflammationLung cancer (organism; 1 paper(s))Lung cancer

Key events

Key eventLevelSupported by
AhR pathway activation
KE:mie-ahr-activation
 molecular chen2025 · ferecatu2010 · harding2021 · lindner2018 · montgomery2020 · schamberger2015
Decreased CFTR function
KE:ke-decreased-cftr
 molecular lambert2014 · liu2024 · nguyen2021
Decreased FOXO3a expression
KE:ke-decreased-foxo3a
 molecular li2021
Decreased intracellular calcium
KE:ke-decreased-intracellular-calcium
 molecular liu2024
Decreased P2Y2R expression
KE:ke-decreased-p2y2r
 molecular liu2024
EGFR activation
KE:ke1-egfr-activation
 molecular chen2025 · ferecatu2010 · ghosh2025 · harding2021 · huang2017 · jiao2022 · kania2014 · liu2012 · lkhagvadorj2020 · ogino2018
ERK1/2 activation
KE:ke-erk-activation
 molecular kim2017
IL-1 inflammatory program activation
KE:ke-il1-inflammation
 molecular chen2025 · montgomery2020
Increased DNA damage
KE:ke-dna-damage
 molecular chen2025
Increased miR-155 expression
KE:ke-increased-mir155
 molecular li2021
Increased oxidative stress
KE:mie-oxidative-stress
 molecular alessandrini2010 · chen2023 · chen2025 · ferecatu2010 · ghosh2025 · han2021 · harding2021 · herath2020 · kim2017 · lagorio2006 · li2018 · li2021 · lindner2018 · liu2009 · liu2018 · ogino2018 · oluwole2013
PI3K/AKT pathway activation
KE:ke-pi3k-akt-activation
 molecular ghosh2025 · liu2018
PI3K/AKT/mTOR signaling activation
KE:mie-pi3k-akt-mtor-activation
 molecular han2021
TLR4 activation
KE:mie-tlr4-activation
 molecular cowley2025
TRP channel activation
KE:mie-trp-channel-activation
 molecular cowley2025
Altered ciliogenesis
KE:ke-altered-ciliogenesis
 cellular jiao2022 · liu2012 · lkhagvadorj2020 · montgomery2020 · schamberger2015
Altered epithelial barrier integrity
KE:ke-epithelial-barrier
 cellular alessandrini2010 · kim2017 · schamberger2015
Alveolar epithelial type II cell hyperplasia
KE:ke-aecii-hyperplasia
 cellular lkhagvadorj2020
Basal cell hyperplasia
KE:ke-basal-cell-hyperplasia
 cellular lkhagvadorj2020
Club cell marker loss
KE:ke-club-cell-loss
 cellular alessandrini2010 · liu2012 · montgomery2020 · schamberger2015
Decreased ASL height
KE:ke-decreased-asl
 cellular lambert2014 · liu2012 · liu2024
Decreased ciliary beat frequency
KE:ke-decreased-cbf
 cellular carvalho2015 · lindner2018 · liu2012
Decreased ciliary function
KE:ke3-impaired-ciliary
 cellular calderon2001 · fujisawa2023 · jiao2022 · liu2012
Decreased MUC5AC expression
KE:ke-muc5ac-decrease
 cellular kania2014
Decreased Muc5b expression
KE:ke-muc5b-decrease
 cellular lindner2018
Disturbed epithelial signal transduction and renewal
KE:ke-disturbed-epithelial-renewal
 cellular gras2013
Goblet cell hyperplasia
KE:ke2-goblet-hyperplasia
 cellular alessandrini2010 · herath2020 · huang2017 · jiao2022 · kania2014 · li2021 · lindner2018 · liu2012 · liu2024 · montgomery2020 · schamberger2015
Impaired alveolar epithelial type I cell differentiation
KE:ke-impaired-aeci-differentiation
 cellular lkhagvadorj2020
Increased autophagy
KE:ke-increased-autophagy
 cellular han2021
Increased cell proliferation
KE:ke-increased-proliferation
 cellular alessandrini2010 · chen2025 · ghosh2025 · li2018
Increased epithelial cell apoptosis
KE:ke-epithelial-apoptosis
 cellular han2021
Increased pro-angiogenic signaling
KE:ke-proangiogenic-signaling
 cellular ghosh2025
Inhibited apoptosis
KE:ke-inhibited-apoptosis
 cellular ferecatu2010
Mucin hypersecretion
KE:ke-mucin-hypersecretion
 cellular carvalho2015 · cowley2025 · gras2013 · herath2020 · huang2017 · jiao2022 · kim2017 · leng2022 · lindner2018 · liu2012 · schamberger2015
Mucus secretory program activation
KE:ke-mucus-metaplasia
 cellular alessandrini2010 · jiao2022 · lkhagvadorj2020
Suppressed apoptosis
KE:ke-suppressed-apoptosis
 cellular ghosh2025
Airway inflammation
KE:ke-airway-inflammation
 tissue alessandrini2010 · chen2025 · cowley2025 · ferecatu2010 · ghosh2025 · gras2013 · han2021 · harding2021 · herath2020 · kim2017 · lindner2018 · liu2009 · liu2012 · liu2018 · liu2024 · ogino2018
Airway remodeling
KE:ke-airway-remodeling
 tissue ferecatu2010 · gras2013
Impaired mucociliary clearance
KE:ke3-impaired-mcc
 tissue calderon2001 · carvalho2015 · fujisawa2023 · lindner2018 · liu2012 · nguyen2021 · schamberger2015
Squamous metaplasia
KE:ke-squamous-metaplasia
 tissue schamberger2015
Decreased lung function
KE:ao-decreased-lung-function
 organ alessandrini2010 · amoabengnti2020 · chen2023 · cuestamosquera2025 · ghosh2025 · han2021 · hart2018 · herath2020 · intpanis2017 · isara2016 · jie2014 · krismanuel2026 · lagorio2006 · leng2022 · li2021 · lindner2018 · liu2009 · liu2012 · liu2024 · ogino2018 · oluwole2013
Increased systemic inflammation
KE:ke-systemic-inflammation
 organism ghosh2025 · han2021 · herath2020 · liu2018 · oluwole2013
Lung cancer
KE:ao-lung-cancer
 organism chen2025

Relationships

UpstreamDownstreamSupportPapers
Increased oxidative stress directly leads to Mucus secretory program activation moderate alessandrini2010
Increased oxidative stress directly leads to Club cell marker loss moderate alessandrini2010
Increased oxidative stress directly leads to / indirectly leads to Airway inflammation strong alessandrini2010 · chen2025 · herath2020 · kim2017 · liu2018
Airway inflammation directly leads to / indirectly leads to Altered epithelial barrier integrity strong alessandrini2010 · kim2017
Decreased ciliary function directly leads to Impaired mucociliary clearance moderate calderon2001 · fujisawa2023 · liu2012
Increased oxidative stress associated with / indirectly leads to Decreased lung function moderate chen2023 · lagorio2006 · li2021 · liu2009 · oluwole2013
Increased oxidative stress directly leads to Increased DNA damage moderate chen2025
Increased oxidative stress directly leads to EGFR activation moderate chen2025
AhR pathway activation directly leads to EGFR activation moderate chen2025 · harding2021
EGFR activation directly leads to Increased cell proliferation moderate chen2025
IL-1 inflammatory program activation directly leads to Airway inflammation moderate chen2025
IL-1 inflammatory program activation indirectly leads to Lung cancer weak chen2025
Increased DNA damage directly leads to Lung cancer moderate chen2025
Increased cell proliferation directly leads to Lung cancer weak chen2025
Airway inflammation indirectly leads to Lung cancer moderate chen2025
TRP channel activation directly leads to Airway inflammation moderate cowley2025
TLR4 activation directly leads to Airway inflammation moderate cowley2025
AhR pathway activation directly leads to Inhibited apoptosis moderate ferecatu2010
EGFR activation directly leads to Inhibited apoptosis weak ferecatu2010
Inhibited apoptosis indirectly leads to Airway inflammation weak ferecatu2010
Inhibited apoptosis indirectly leads to Airway remodeling weak ferecatu2010
PI3K/AKT pathway activation indirectly leads to Suppressed apoptosis moderate ghosh2025
PI3K/AKT pathway activation indirectly leads to Increased cell proliferation moderate ghosh2025
PI3K/AKT pathway activation indirectly leads to Increased pro-angiogenic signaling moderate ghosh2025
EGFR activation directly leads to PI3K/AKT pathway activation weak ghosh2025
Disturbed epithelial signal transduction and renewal indirectly leads to Airway remodeling weak gras2013
PI3K/AKT/mTOR signaling activation directly leads to Increased autophagy strong han2021
Increased autophagy directly leads to Increased epithelial cell apoptosis moderate han2021
Increased epithelial cell apoptosis indirectly leads to Decreased lung function moderate han2021
Increased oxidative stress indirectly leads to Increased epithelial cell apoptosis weak han2021
EGFR activation indirectly leads to Airway inflammation weak harding2021
AhR pathway activation indirectly leads to Airway inflammation moderate harding2021
Airway inflammation associated with Increased systemic inflammation weak herath2020 · liu2018
Airway inflammation indirectly leads to Goblet cell hyperplasia moderate herath2020
Goblet cell hyperplasia directly leads to Mucin hypersecretion moderate herath2020 · liu2012
Mucin hypersecretion associated with / indirectly leads to Decreased lung function moderate herath2020 · leng2022 · liu2012
Airway inflammation directly leads to / indirectly leads to Decreased lung function moderate herath2020 · liu2024 · ogino2018
EGFR activation directly leads to Mucin hypersecretion strong huang2017 · jiao2022 · liu2012
EGFR activation directly leads to Goblet cell hyperplasia moderate jiao2022
Increased oxidative stress directly leads to ERK1/2 activation strong kim2017
ERK1/2 activation directly leads to Altered epithelial barrier integrity strong kim2017
Altered epithelial barrier integrity directly leads to Mucin hypersecretion strong kim2017
Decreased CFTR function directly leads to Decreased ASL height moderate lambert2014 · liu2024
Increased oxidative stress indirectly leads to Increased cell proliferation moderate li2018
Increased miR-155 expression directly leads to Decreased FOXO3a expression strong li2021
Decreased FOXO3a expression directly leads to Increased oxidative stress strong li2021
Mucin hypersecretion directly leads to Decreased ciliary beat frequency weak lindner2018
Decreased Muc5b expression indirectly leads to Impaired mucociliary clearance weak lindner2018
Goblet cell hyperplasia directly leads to Impaired mucociliary clearance moderate liu2012
Airway inflammation indirectly leads to Mucin hypersecretion moderate liu2012
Goblet cell hyperplasia directly leads to Club cell marker loss moderate liu2012
Altered ciliogenesis directly leads to Decreased ciliary function moderate liu2012
Decreased ciliary beat frequency directly leads to Impaired mucociliary clearance moderate liu2012
Decreased ASL height directly leads to Impaired mucociliary clearance moderate liu2012
Impaired mucociliary clearance indirectly leads to Airway inflammation weak liu2012
Increased oxidative stress directly leads to PI3K/AKT pathway activation moderate liu2018
PI3K/AKT pathway activation directly leads to Airway inflammation moderate liu2018
Decreased P2Y2R expression directly leads to Decreased intracellular calcium moderate liu2024
Decreased intracellular calcium indirectly leads to Decreased CFTR function weak liu2024
Decreased P2Y2R expression directly leads to Decreased CFTR function moderate liu2024
Decreased CFTR function indirectly leads to Airway inflammation moderate liu2024
EGFR activation directly leads to Altered ciliogenesis moderate lkhagvadorj2020
EGFR activation directly leads to Basal cell hyperplasia moderate lkhagvadorj2020
EGFR activation directly leads to Alveolar epithelial type II cell hyperplasia moderate lkhagvadorj2020
EGFR activation indirectly leads to Mucus secretory program activation weak lkhagvadorj2020
EGFR activation indirectly leads to Impaired alveolar epithelial type I cell differentiation weak lkhagvadorj2020
AhR pathway activation directly leads to IL-1 inflammatory program activation moderate montgomery2020
IL-1 inflammatory program activation directly leads to Goblet cell hyperplasia moderate montgomery2020
Decreased CFTR function directly leads to Impaired mucociliary clearance weak nguyen2021
Increased oxidative stress associated with Increased systemic inflammation weak oluwole2013
Altered ciliogenesis indirectly leads to Impaired mucociliary clearance weak schamberger2015