Genome-Wide Transcriptional Response During the Development of Bleomycin-Induced Pulmonary Fibrosis in Sprague-Dawley Rats

Abstract

Pulmonary fibrosis is a common consequence of many lung diseases and a leading cause of morbidity and mortality. The molecular mechanisms underlying the development of pulmonary fibrosis remain poorly understood. One model used successfully to study pulmonary fibrosis over the past few decades is the bleomycin-induced pulmonary fibrosis model. We aimed to identify the genes associated with fibrogenesis using an Affymetrix GeneChip system in a bleomycin-induced rat model for pulmonary fibrosis. To confirm fibrosis development, several analyses were performed, including cellular evaluations using bronchoalveolar lavage fluid, measurement of lactate dehydrogenase activity, and histopathological examinations. Common aspects of pulmonary fibrosis such as prolonged inflammation, immune cell infiltration, emergence of fibroblasts, and deposition of extracellular matrix and connective tissue elements were observed. Global gene expression analysis revealed significantly altered expression of genes (≥ 1.5-fold, p < 0.05.) in a time-dependent manner during the development of pulmonary fibrosis. Our results are consistent with previous results of well-documented gene expression. Interestingly, the expression of triggering receptor expressed on myeloid cells 2 (Trem2) , secreted phosphoprotein 1 (Spp1) , and several proteases such as Tpsab1, Mcpt1, and Cma1 was considerably induced in the lung after bleomycin treatment, despite little evidence that they are involved in pulmonary fibrogenesis. These data will aid in our understanding of fibrogenic mechanisms and contribute to the identification of candidate biomarkers of fibrotic disease development.

Maximizing Small Biopsy Patient Samples: Unified RNA-Seq Platform Assessment of over 120,000 Patient Biopsies

“…Other, rarer fusions were also identified, including GAS7-MYH1 and ZCCHC8-RSRC2 , each of which were identified in 4 ILD samples and have been reported previously in cancer samples ( GAS7-MYH1 in lung and stomach adenocarcinoma, and ZCCHC8-RSRC2 in multiple cancers) [ 52 ]. Interestingly, expression of MYH1 has previously been found to be upregulated in the bleomycin mouse model of idiopathic pulmonary fibrosis (IPF) [ 53 ]. Overall, although fusions are rare in ILD, these data indicate the potential for revealing molecular information that may be relevant to disease manifestation.…”

Local inflammation alters the lung disposition of a drug loaded pegylated liposome after pulmonary dosing to rats

“…The chronic bleomycin model of lung inflammation (producing lung inflammation that persists for more than 8 days) was initially optimised in house based on previously published procedures [26,27]. A single bleomycin dose of 2.8 mg/kg delivered via liquid intratracheal instillation (as previously described [11,17]) in a volume of 100 ul sterile saline was optimally found to produce significant lung inflammation over 8 days without adversely impacting the health and general wellbeing of rats.…”

LC50 Determination of tert-Butyl Acetate using a Nose Only Inhalation Exposure in Rats

“…Further, with regard to the total cell count and differential inflammatory cell count in BALF, there was no significant difference among the groups before and after exposure. Previous studies have shown that when the lung is exposed to a toxic material, inflammations generally occur after 2 days and manifest after 7 days of exposure (Yang et al, 2008 ; Park et al, 2010) .…”