Inhibiting TGFβ1 has a protective effect on mouse bone marrow suppression following ionizing radiation exposure in vitro.
Ionizing radiation (IR) causes not only acute tissue damage but also residual bone marrow (BM) suppression. The induction of residual BM injury is primarily attributable to the induction of reactive oxygen species (ROS) pressure in hematopoietic cells. In this study, we examined if SB431542, a transforming growth factor β1 (TGFβ1) inhibitor, can mitigate IR-induced BM suppression in vitro. Our results showed that treatment with SB431542 protected mice bone marrow mononuclear cells (BMMNCs), hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs) from IR-induced suppression using cell viability assays, clonogenic assays and competitive repopulation assays. Moreover, expression of gene-related ROS production in hematopoietic cells was analyzed. The expression of NOX1, NOX2 and NOX4 was increased in irradiated BMMNCs, and that of NOX2 and NOX4 was reduced by SB431542 treatment. Therefore, the results from this study suggest that SB431542, a TGFβ1 inhibitor, alleviates IR-induced BM suppression at least in part via inhibiting IR-induced NOX2 and NOX4 expression.
Department of Radiation Oncology, Tianjin Union Medical Center, No.190 Jieyuan Road, Nankai District, Tianjin, China.
Heng
H
Zhang
Ying-Ai
YA
Wang
Aimin
A
Meng
Hao
H
Yan
Xinzhuo
X
Wang
Jingxiu
J
Niu
Jin
J
Li
Hui
H
Wang
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects*; D002470:Cell Survival; D004149:Dioxoles / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000528:radiation effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D011832:Radiation Injuries / Q000517:prevention & control*; D011839:Radiation, Ionizing; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors*
C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; D008562:Membrane Glycoproteins; D053773:Transforming Growth Factor beta1; D009247:NADH, NADPH Oxidoreductases; C488842:Cybb protein, mouse; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C000614711:NOX1 protein, mouse; C422943:Nox4 protein, mouse
NADPH oxidase; TGFβ1; bone marrow suppression; ionizing radiation