Differential gene analysis during the development of obliterative bronchiolitis in a murine orthotopic lung transplantation model: A comprehensive transcriptome-based analysis

Abstract

Background Obliterative bronchiolitis (OB) is a known issue during minor histocompatibility antigen (mHA) disparity during lung transplantation. This study evaluated gene expression in a murine orthotropic lung transplantation model using microarray analysis. Methods Left lungs from C57BL/10(H-2 b) donor mice were transplanted into mHA-mismatched C57BL/6(H-2 b) recipient mice. Three groups (OB, non-OB, and sham controls) were confirmed pathologically and analyzed. Gene expression changes in the lung grafts were determined by microarray and immunohistochemical staining, and genes were verified by quantitative PCR in the lungs and mediastinal lymph nodes (LNs). Results A total of 1343 genes were upregulated in the OB lungs compared to the sham group. Significant upregulation was observed for genes related to innate, e.g. Tlr2 and CCL3 and adaptive immunity, e.g. H2-ab1 and Il-21. Positive labeling for MHC class II antigen was observed in the bronchial epithelium of OB accompanied with B cells. We found increased Tlr2, Ccl3, H2-ab1, Il-21, Ighg3, Ifng, and Pdcd1 mRNA expression in the OB lung, and increased Il-21, Ighg3, and Pdcd1 expression in the OB LNs.

Anti-CD20 Antibody and Calcineurin Inhibitor Combination Therapy Effectively Suppresses Antibody-Mediated Rejection in Murine Orthotopic Lung Transplantation

“…Consequently, treatment options for AMR are limited, and the efficacy of each drug has been poorly reported. Using rodent models of lung transplantation, our laboratory has previously reported antigen-antibody reactions, such as anti-collagen type V antibody [13], minor antigen [14,15], and complement activation [16,17].…”

Transcriptome analysis reveals the impact of NETs activation on airway epithelial cell EMT and inflammation in bronchiolitis obliterans

“…Specifically, bioinformatics analyses derived from next-generation sequencing technologies can offer researchers a more comprehensive understanding of the identification of molecular mechanisms crucial for diseases pathogenesis and progression. For example, research in BO recently had suggested the involvement of innate immune reactions in BO pathogenesis, in which the combinational analysis of transcriptomic sequencing and bioinformatics had provided the means to better identify the gene and its respective signaling pathways in BO pathogenesis 5 , 6 . Moreover, by analyzing and comparing existing BO-related transcriptomic data from various studies, researchers may gain opportunities to discover novel target, that was previously neglected in the study of BO.…”

Identification of Hub Genes in the Pathogenesis of Bronchiolitis Obliterans via Bioinformatic Analysis and Experimental Verification

“…4 Previous studies that rely on transcriptomic data analysis using bioinformatics approaches have also succeeded in yielding promising results, specifically by exploring BO molecular mechanisms. [5][6][7] However, identification and verification of distinct molecular markers are still lacking, primarily because of limitations such as small sample sizes, inadequate transcriptome data analysis, and the absence of verification processes.…”