TY - JOUR
T1 - Developmental pathways in the pathogenesis of lung fibrosis
AU - Chanda, Diptiman
AU - Otoupalova, Eva
AU - Smith, Samuel R.
AU - Volckaert, Thomas
AU - De Langhe, Stijn P.
AU - Thannickal, Victor J.
N1 - Funding Information:
This work was supported by NIH grants (USA) , P01 HL114470 and R01 AG046210 ; and by VA Merit Award (USA) , IK2 BX001477-01 (to VJT), and NIH grants , R01 HL126732 , HL132156 (to SDL).
Publisher Copyright:
© 2018
PY - 2019/2
Y1 - 2019/2
N2 - Idiopathic pulmonary fibrosis (IPF) is a progressive and terminal lung disease with no known cure. IPF is a disease of aging, with median age of diagnosis over 65 years. Median survival is between 3 and 5 years after diagnosis. IPF is characterized primarily by excessive deposition of extracellular matrix (ECM) proteins by activated lung fibroblasts and myofibroblasts, resulting in reduced gas exchange and impaired pulmonary function. Growing evidence supports the concept of a pro-fibrotic environment orchestrated by underlying factors such as genetic predisposition, chronic injury and aging, oxidative stress, and impaired regenerative responses may account for disease development and persistence. Currently, two FDA approved drugs have limited efficacy in the treatment of IPF. Many of the genes and gene networks associated with lung development are induced or activated in IPF. In this review, we analyze current knowledge in the field, gained from both basic and clinical research, to provide new insights into the disease process, and potential approaches to treatment of pulmonary fibrosis.
AB - Idiopathic pulmonary fibrosis (IPF) is a progressive and terminal lung disease with no known cure. IPF is a disease of aging, with median age of diagnosis over 65 years. Median survival is between 3 and 5 years after diagnosis. IPF is characterized primarily by excessive deposition of extracellular matrix (ECM) proteins by activated lung fibroblasts and myofibroblasts, resulting in reduced gas exchange and impaired pulmonary function. Growing evidence supports the concept of a pro-fibrotic environment orchestrated by underlying factors such as genetic predisposition, chronic injury and aging, oxidative stress, and impaired regenerative responses may account for disease development and persistence. Currently, two FDA approved drugs have limited efficacy in the treatment of IPF. Many of the genes and gene networks associated with lung development are induced or activated in IPF. In this review, we analyze current knowledge in the field, gained from both basic and clinical research, to provide new insights into the disease process, and potential approaches to treatment of pulmonary fibrosis.
KW - Antagonistic pleiotropy
KW - Development
KW - Fibroblast growth factor (FGF)
KW - Fibrosis
KW - Hippo
KW - Lung
KW - Notch
KW - Platelet derived growth factor (PDGF)
KW - Sonic hedgehog (SHH)
KW - Transforming growth factor-β (TGF-β)
KW - Wnt
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U2 - 10.1016/j.mam.2018.08.004
DO - 10.1016/j.mam.2018.08.004
M3 - Review article
C2 - 30130563
AN - SCOPUS:85054349820
VL - 65
SP - 56
EP - 69
JO - Molecular Aspects of Medicine
JF - Molecular Aspects of Medicine
SN - 0098-2997
ER -