Deconvolution of RNA-Seq Analysis of Hyperbaric Oxygen-Treated Mice Lungs Reveals Mesenchymal Cell Subtype Changes

Abstract

Hyperbaric oxygen (HBO) is widely applied to treat several hypoxia-related diseases. Previous studies have focused on the immediate effect of HBO-exposure induced oxidative stress on the lungs, but knowledge regarding the chronic effects from repetitive HBO exposure is limited, especially at the gene expression level. We found that repetitive HBO exposure did not alter the morphology of murine lungs. However, by deconvolution of RNA-seq from those mice lungs using CIBERSORTx and the expression profile matrices of 8 mesenchymal cell subtypes obtained from bleomycin-treated mouse lungs, we identify several mesenchymal cell subtype changes. These include increases in Col13a1 matrix fibroblasts, mesenchymal progenitors and mesothelial cell populations and decreases in lipofibroblasts, endothelial and Pdgfrb high cell populations. Our data suggest that repetitive HBO exposure may affect biological processes in the lungs such as response to wounding, extracellular matrix, vasculature development and immune response.

Hyperbaric Oxygen Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Mice

“…To extend these findings, a bleomycin-induced pulmonary fibrosis mouse model was used to evaluate the effect of repetitive HBO exposure on pulmonary fibrosis. Building on our previous report (Yuan et al, 2020), we provide evidence that HBO exposure attenuates bleomycin-induced pulmonary fibrosis in mice. In vitro, HBO exposure could reverse, at least partially, transforming growth factor (TGF)-β-induced fibroblast activation.…”

“…In another report, HBO exposure reduced radiation-induced side effects including fibrosis in a rat bladder irradiation model (Oscarsson et al, 2017). Mechanistically, our recent study suggested that repetitive HBO exposure may affect biological processes in mice lungs such as response to wounding and ECM (Yuan et al, 2020). To extend these findings, a bleomycin-induced pulmonary fibrosis mouse model was used to evaluate the effect of repetitive HBO exposure on pulmonary fibrosis.…”

“…The RNA-seq data analyzed were based on our previous study (Yuan et al, 2020) (GSE143348). Briefly, lungs were collected from control mice or HBO-treated mice that were repetitively exposed to 2.5 ATA HBO, 90 min/time, once a day for 11 consecutive days.…”

“…A hyperbaric chamber designed for small animal research was used for HBO exposure, as described previously (Yuan et al, 2020). Briefly, after the chamber was flushed with pure oxygen for 5 min, the pressure ramped up to 2.5 ATA (1.5 atm) by inflating 100% oxygen slowly in 5 min, then sustained at 2.5 ATA for 90 min, and finally decompressed slowly in 5 min.…”

“…Our previous study suggested that repetitive HBO treaments may affect biological processes in the lungs, such as response to wounding and extracellular matrix (Yuan et al, 2020). We reported that in the down-regulated genes in mice lungs following repetitive HBO exposure (GSE143348), enriched terms for cellular component classification including the "collagen containing extracellular matrix" and "extracellular matrix component," suggesting that the extracellular matrix may be affected (Yuan et al, 2020). These findings were also reflected using the REVIGO TreeMap, which found the "extracellular matrix" as a GO-enriched term (Figure 1A).…”