The Promising Therapeutic Approaches for Radiation-Induced Pulmonary Fibrosis: Targeting Radiation-Induced Mesenchymal Transition of Alveolar Type II Epithelial Cells
Abstract
:1. Introduction
2. Radiation-Induced EMT Promotes RIPF
2.1. RIPF
2.2. Radiation-Induced EMT
3. Signaling Pathway Involved in EMT of AT2 Cell in RIPF
3.1. TGF-β Signaling Pathway
3.2. Tyrosine Kinases Pathway
3.3. PI3K/AKT Signaling Pathway
3.4. Epigenetic Factors (MicroRNAs)
4. Therapy Strategy of RIPF by Targeting EMT
4.1. Current Clinical Situation of Pulmonary Fibrosis
4.2. Pre-Clinical Treatment of RIPF
4.2.1. Targeting TGF-β Signaling Pathway
4.2.2. Targeting Growth Factors
4.2.3. Additional Targets
Mechanism | Name | Structural Formula | Type | Target | Ref. |
---|---|---|---|---|---|
ROS | Amifostine | Organic thiophosphate | Scavenging free radicals | [86,87] | |
SOD-TAT | Recombinant protein | Oxidative damage | [88] | ||
TGF-β signaling pathway | LY2109761 | Quinoline derivatives | TβR1 inhibitor | [89] | |
Galunisertib | Pyrrolopyrazole | TβR1 inhibitor | [90] | ||
SB203580 | Imidazoles | TβR1 inhibitor | [91] | ||
WP631 | Bisintercalating anthracycline | TβR1 inhibitor | [91] | ||
SM16 | Antibody | TβR1 inhibitor | [92] | ||
Halofuginone | Quinazolinone alkaloid | Smad2/3 phosphorylation | [94] | ||
Verbascoside | Glucosides | Smad2/3 phosphorylation Increasing Smad7 | [95] | ||
Tyrosine kinase pathway | Flufenidone | Anti-fibrotic drug | CTGF | [99] | |
FG-3019 | Recombinant antibody | CTGF | [41] | ||
Imatinib | Antineoplastic agent | PDGF | [101] | ||
SU9518 | Small molecule | VEGF PDGF | [38,39] | ||
Addition | 2-ME | 17β-hydroxy steroid | PI3K/AKT HIF-1α | [103] | |
J2 | Small molecule | IkBa-NFkB HSP-27 | [104] | ||
MyD88 | Recombinant protein | NF-κB activation | [105] |
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Wang, P.; Yan, Z.; Zhou, P.-K.; Gu, Y. The Promising Therapeutic Approaches for Radiation-Induced Pulmonary Fibrosis: Targeting Radiation-Induced Mesenchymal Transition of Alveolar Type II Epithelial Cells. Int. J. Mol. Sci. 2022, 23, 15014. https://doi.org/10.3390/ijms232315014
Wang P, Yan Z, Zhou P-K, Gu Y. The Promising Therapeutic Approaches for Radiation-Induced Pulmonary Fibrosis: Targeting Radiation-Induced Mesenchymal Transition of Alveolar Type II Epithelial Cells. International Journal of Molecular Sciences. 2022; 23(23):15014. https://doi.org/10.3390/ijms232315014
Chicago/Turabian StyleWang, Ping, Ziyan Yan, Ping-Kun Zhou, and Yongqing Gu. 2022. "The Promising Therapeutic Approaches for Radiation-Induced Pulmonary Fibrosis: Targeting Radiation-Induced Mesenchymal Transition of Alveolar Type II Epithelial Cells" International Journal of Molecular Sciences 23, no. 23: 15014. https://doi.org/10.3390/ijms232315014