Radiation-induced pulmonary fibrosis: roles of therapy-induced senescence and microRNAs.
Int J Radiat Biol
; 99(7): 1027-1036, 2023.
Article
in En
| MEDLINE
| ID: mdl-36763093
ABSTRACT
PURPOSE:
Progressive, irreversible radiation-induced pulmonary fibrosis (RIPF) is a clinically significant intermediate- to a late-occurring side effect of radiotherapy. Known mechanisms of RIPF include oxidative stress-induced activation of TGF-ß with activation of SMAD signaling, TNF-α elaboration, and activation of the Angiotensin Converting Enzyme (ACE) mediated production of angiotensin II with resulting activation of profibrotic cytokine signaling and vasoconstriction. The pioneering work of John Moulder, to whom this paper is dedicated, and several of his colleagues demonstrated that inhibiting the conversion of ACE with drugs such as Captopril, Enalapril, and Losartan can ameliorate radiation fibrosis in various tissues. While this work led several groups to probe mechanism-based pharmacological mitigation of RIPF, in this article, we explore and discuss the roles of microRNAs (miRNA) and therapy-induced senescence (TIS) in the pathogenesis of and potential biomarkers for RIPF.CONCLUSION:
Our analysis of the published literature in the last decade on RIPF, miRNA, and TIS identifies TIS as a mechanism in the onset and progression of RIPF, which is regulated through several miRNAs. This work may lead to the discovery and development of the next generation of miRNA therapeutics and/or the repurposing of approved pharmaceutical agents and the development of early biomarker panels to predict RIPF.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pulmonary Fibrosis
/
Radiation Injuries
/
MicroRNAs
Type of study:
Etiology_studies
Limits:
Humans
Language:
En
Journal:
Int J Radiat Biol
Journal subject:
RADIOLOGIA
Year:
2023
Document type:
Article
Affiliation country:
Estados Unidos