TY - JOUR
T1 - MiRNA-Mediated Fibrosis in the Out-of-Target Heart following Partial-Body Irradiation
AU - Tanno, Barbara
AU - Novelli, Flavia
AU - Leonardi, Simona
AU - Merla, Caterina
AU - Babini, Gabriele
AU - Giardullo, Paola
AU - Kadhim, Munira
AU - Traynor, Damien
AU - Medipally, Dinesh K.R.
AU - Meade, Aidan D.
AU - Lyng, Fiona M.
AU - Tapio, Soile
AU - Marchetti, Luca
AU - Saran, Anna
AU - Pazzaglia, Simonetta
AU - Mancuso, Mariateresa
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2022/7
Y1 - 2022/7
N2 - Recent reports have shown a link between radiation exposure and non-cancer diseases such as radiation-induced heart disease (RIHD). Radiation exposures are often inhomogeneous, and out-of-target effects have been studied in terms of cancer risk, but very few studies have been carried out for non-cancer diseases. Here, the role of miRNAs in the pathogenesis of RIHD was investigated. C57Bl/6J female mice were whole- (WBI) or partial-body-irradiated (PBI) with 2 Gy of X-rays or sham-irradiated (SI). In PBI exposure, the lower third of the mouse body was irradiated, while the upper two-thirds were shielded. From all groups, hearts were collected 15 days or 6 months post-irradiation. The MiRNome analysis at 15 days post-irradiation showed that miRNAs, belonging to the myomiR family, were highly differentially expressed in WBI and PBI mouse hearts compared with SI hearts. Raman spectral data collected 15 days and 6 months post-irradiation showed biochemical differences among SI, WBI and PBI mouse hearts. Fibrosis in WBI and PBI mouse hearts, indicated by the increased deposition of collagen and the overexpression of genes involved in myofibroblast activation, was found 6 months post-irradiation. Using an in vitro co-culture system, involving directly irradiated skeletal muscle and unirradiated ventricular cardiac human cells, we propose the role of miR-1/133a as mediators of the abscopal response, suggesting that miRNA-based strategies could be relevant for limiting tissue-dependent reactions in non-directly irradiated tissues.
AB - Recent reports have shown a link between radiation exposure and non-cancer diseases such as radiation-induced heart disease (RIHD). Radiation exposures are often inhomogeneous, and out-of-target effects have been studied in terms of cancer risk, but very few studies have been carried out for non-cancer diseases. Here, the role of miRNAs in the pathogenesis of RIHD was investigated. C57Bl/6J female mice were whole- (WBI) or partial-body-irradiated (PBI) with 2 Gy of X-rays or sham-irradiated (SI). In PBI exposure, the lower third of the mouse body was irradiated, while the upper two-thirds were shielded. From all groups, hearts were collected 15 days or 6 months post-irradiation. The MiRNome analysis at 15 days post-irradiation showed that miRNAs, belonging to the myomiR family, were highly differentially expressed in WBI and PBI mouse hearts compared with SI hearts. Raman spectral data collected 15 days and 6 months post-irradiation showed biochemical differences among SI, WBI and PBI mouse hearts. Fibrosis in WBI and PBI mouse hearts, indicated by the increased deposition of collagen and the overexpression of genes involved in myofibroblast activation, was found 6 months post-irradiation. Using an in vitro co-culture system, involving directly irradiated skeletal muscle and unirradiated ventricular cardiac human cells, we propose the role of miR-1/133a as mediators of the abscopal response, suggesting that miRNA-based strategies could be relevant for limiting tissue-dependent reactions in non-directly irradiated tissues.
KW - Raman spectroscopy
KW - abscopal effect
KW - cardiac fibrosis
KW - miR-1
KW - miRNome
KW - mir-133a
UR - http://www.scopus.com/inward/record.url?scp=85136370219&partnerID=8YFLogxK
U2 - 10.3390/cancers14143463
DO - 10.3390/cancers14143463
M3 - Article
AN - SCOPUS:85136370219
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 14
M1 - 3463
ER -