Comparison of acute proton, photon, and low-dose priming effects on genes associated with extracellular matrix and adhesion molecules in the lungs

Abstract

BackgroundCrew members on space missions inevitably are exposed to low background radiation and can receive much higher doses during solar particle events (SPE) that consist primarily of protons. Ionizing radiation could cause lung pathologies. Cell adhesion molecules (CAM) are believed to participate in fibrogenesis. Interactions between CAM and extracellular matrix (ECM) affect epithelial repair mechanisms in the lung. However, there are very limited data on biological effects of protons on normal lung tissue. Numerous reports have shown that exposure to low-dose/low-dose-rate (LDR) radiation can result in radioadaptation that renders cells more resistant to subsequent acute radiation. The goal of this study was to compare expression of genes associated with ECM and CAM, as well as critical profibrotic mediators, in mouse lungs after acute irradiation with photons and protons, and also determine whether pre-exposure to LDR γ-rays induces an adaptive effect.ResultsOverall, a marked difference was present in the proton vs. photon groups in gene expression. When compared to 0 Gy, more genes were affected by protons than by photons at both time points (11 vs. 6 on day 21 and 14 vs. 8 on day 56), and all genes affected by protons were upregulated. Many genes were modulated by LDR γ-rays when combined with photons or protons. Col1a1, mmp14, and mmp15 were significantly upregulated by all radiation regimens on day 21. Similarly, the change in expression of profibrotic proteins was also detected after acute and combination irradiation.ConclusionThese data show that marked differences were present between acutely delivered protons and photons in modulating genes, and the effect of protons was more profound than that of photons. Pre-exposure to LDR γ-rays ‘normalized’ some genes that were modified by acute irradiation.

Radiation Type- and Dose-Specific Transcriptional Responses across Healthy and Diseased Mammalian Tissues

“…For database construction, we performed text mining in PubMed, using appropriate keywords across studies that experimentally address the overall effect of five high- and low-LET radiation types of interest in a broad range of mammalian cell types, including human, mouse and rat study model systems. The database includes 7436 entries, with a total of 3730 unique genes derived from 14 tissues/cell lines [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ]. For each entry, the following information was provided: Differential expression of genes: The expression status of the corresponding genes (i.e., up or downregulated in irradiated compared to non-irradiated tissue/cell control groups).…”

Pathogenesis of Type 2 Epithelial to Mesenchymal Transition (EMT) in Renal and Hepatic Fibrosis

“…Additionally, hepatic cirrhosis has become a main cause of hepatocellular carcinoma. To study hepatic cirrhosis, various animal models have been utilized [ 102 ]. We have used toxin-induced rat models: thioacetamide (TAA)-induced and α-naphthylisothiocyanate (ANIT)-induced hepatic fibrosis; the former develops centrilobular injury/necrosis and subsequent fibrosis, the latter induced peri-biliary fibrosis in the Glisson’ sheath [ 103 , 104 ].…”

Expression of Airway Remodeling Proteins in Mast Cell Activated by TGF-β Released in OVA-Induced Allergic Responses and Their Inhibition by Low-Dose Irradiation or 8-oxo-dG

“…Irradiation-induced ECM-associated gene alterations are caused by different total dose and/or dose-rate regimens in mouse skin (23). Low-dose irradiation also up-regulates the expression of ECMrelated genes in murine cells (24) and lung tissues (25), but it inhibits mast cell activation through suppression of FceRI (26). In contrast, high-dose irradiation mediates degradation of collagen type IV as a major ECM compartment of the blood-brain barrier (BBB) basement membrane by an imbalance of MMP2 and TIMP2 in brain (27).…”