Response of extracellular matrix regulators in mouse lung after exposure to photons, protons and simulated solar particle event protons.
This study compared the effects of photons (gamma rays), protons and simulated solar particle event protons (sSPE) on the expression of profibrotic factors/extracellular matrix (ECM) regulators in lung tissue after whole-body irradiation. TGF-beta1, matrix metalloproteinase 2 and 9 (MMP-2, -9), and tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1, -2) were assessed on days 4 and 21 in lungs from C57BL/6 mice exposed to 0 Gy or 2 Gy photons (0.7 Gy/min), protons (0.9 Gy/min) and sSPE (0.056 Gy/h). RT-PCR, histological and immunohistochemical techniques were used. The most striking changes included (1) up-regulation of TGF-beta1 by photons and sSPE, but not protons, at both times, (2) MMP-2 enhancement by photons and sSPEs, (3) TIMP-1 up-regulation by photons at both times, and (4) more collagen accumulation after exposure to either photons or sSPE than after exposure to protons. The findings demonstrate that expression of important ECM regulators was highly dependent upon the radiation regimen as well as the time after exposure. The data further suggest that irradiation during an SPE may increase an astronaut's risk for pulmonary complications. The greater perturbations after photon exposure compared to proton exposure have clinical implications and warrant further investigation.
Tian
Jian
J
Department of Radiation Medicine, Radiation Research Laboratories, Loma Linda University and Medical Center, Loma Linda, CA 92354, USA.
Pecaut
Michael J
MJ
Coutrakon
George B
GB
Slater
James M
JM
Gridley
Daila S
DS
D000818:Animals; D003094:Collagen / Q000378:metabolism; D003359:Cosmic Radiation; D016326:Extracellular Matrix Proteins / Q000378:metabolism / Q000528:radiation effects*; D005260:Female; D005720:Gamma Rays; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017785:Photons; D011522:Protons; D012333:RNA, Messenger / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D016326:Extracellular Matrix Proteins; D011522:Protons; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9