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Jinhee Choi, University of Seoul, Republic of Korea
Nivedita Chatterjee, University of Seoul, India
Jaeseong Jeong, University of Seoul, Republic of Korea
Youngho Kim, University of Seoul, Republic of Korea
Ji-yeon Rho, Knoell Korea, Republic of Korea
Eun-Young Kim, Kyung Hee University, Republic of Korea
Seung Min Oh, Hoseo University, Republic of Korea
Natàlia Garcia-Reyero, Mississippi State University, USA
Edward J. Perkins, U.S. Army Engineer Research and Development Center, USA
Lyle D. Burgoon, U.S. Army Engineer Research and Development Center, USA
Point of Contact
Jinhee Choi (email point of contact)
- Jinhee Choi
|Author status||OECD status||OECD project||SAAOP status|
|Under development: Not open for comment. Do not cite||Under Development||1.54||Included in OECD Work Plan|
This AOP was last modified on March 18, 2018 09:52
|Inactivation of PPARγ||December 26, 2017 02:12|
|Activation of TGF-β signaling||February 15, 2017 02:45|
|Expression of Collagen||February 15, 2017 02:54|
|Collagen Deposition||February 15, 2017 02:55|
|Lung fibrosis||December 26, 2017 02:10|
|Activation of PPARγ||March 18, 2018 09:40|
|Increase, Inflammation||September 16, 2017 10:14|
|Induction, Epithelial Mesenchymal Transition||July 26, 2017 19:11|
|Inactivation of PPARγ leads to Activation of TGF-β signaling||February 15, 2017 02:57|
|Activation of TGF-β signaling leads to Increase, Inflammation||March 18, 2018 09:46|
|Activation of TGF-β signaling leads to EMT||March 18, 2018 09:49|
|Activation of PPARγ leads to Increase, Inflammation||March 18, 2018 09:45|
|Increase, Inflammation leads to Expression of Collagen||March 18, 2018 09:47|
|Increase, Inflammation leads to EMT||March 18, 2018 09:50|
|Expression of Collagen leads to Collagen Deposition||February 15, 2017 02:58|
|Collagen Deposition leads to Lung fibrosis||February 15, 2017 02:58|
|EMT leads to Lung fibrosis||March 18, 2018 09:50|
Pulmonary fibrosis is a respiratory disease in which scars are formed in the lung tissues, leading to serious breathing problems. It is an immunological process that is known to be regulated by the immune modulator Peroxisome proliferator-activated receptors γ (PPARγ) and transforming growth factor β (TGF-β). PPARγ ligands antagonize the profibrotic effects of TGF-β in which induce differentiation of fibroblasts to myofibroblasts, a critical effector cell in fibrosis. These sequential set of events are described in this Adverse Outcome Pathway (AOP). The molecular initiating event (MIE) is inactivation of PPARγ which leads to TGF-β inactivation, a key event (KE) at molecular level. Next, key event at cellular level is differentiation of Myofibroblast and expression of collagen gene by activated TGF-β signaling pathway. Differentiated myofibroblast subsequently produce α-smooth muscle actin (α-SMA) and overexpressed collagen deposits in lung tissue. This consecutive KE resulting in the acquisition of the accumulation of excess fibrous connective tissue, the adverse outcome on pulmonary fibrosis. Scar formation, the accumulation of excess fibrous connective tissue (the process called fibrosis), leads to thickening of the walls, and causes reduced oxygen supply in the blood. As a consequence patients suffer from perpetual shortness of breath.
Summary of the AOP
Events: Molecular Initiating Events (MIE)
|Sequence||Type||Event ID||Title||Short name|
|1||MIE||1270||Inactivation of PPARγ||Inactivation of PPARγ|
|2||MIE||1507||Activation of PPARγ||Activation of PPARγ|
|3||KE||1271||Activation of TGF-β signaling||Activation of TGF-β signaling|
|4||KE||149||Increase, Inflammation||Increase, Inflammation|
|5||KE||1273||Expression of Collagen||Expression of Collagen|
|6||KE||1275||Collagen Deposition||Collagen Deposition|
|7||KE||1457||Induction, Epithelial Mesenchymal Transition||EMT|
|8||AO||1276||Lung fibrosis||Lung fibrosis|
Relationships Between Two Key Events
(Including MIEs and AOs)
Life Stage Applicability
|All life stages|
|Homo sapiens||Homo sapiens||NCBI|
Overall Assessment of the AOP
Domain of Applicability
Essentiality of the Key Events
Considerations for Potential Applications of the AOP (optional)
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