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Objective To study the expression profile and possible roles of ferroptosis-related genes in a bleomycin-induced murine model of pulmonary fibrosis. Methods Twelve 6-7-week-old male C57BL/6 mice were randomly divided into model group and control group, 6 in each group. The model group received nasal inhalation of bleomycin, while the control group was given an equal volume of normal saline. Lung tissues were collected 3 weeks after modeling. Pathological changes and collagen deposition in lungs were observed by HE and Masson staining. Prussian blue staining was used to observe the level of iron accumulation in lung tissue. Total RNA was extracted for PCR Array to identify ferroptosis-related differentially expressed genes (DEGs). Functional analysis for DEGs was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Expression levels of DEGs were verified by RT-qPCR analysis. Results Compared with control group, fibrosis and obvious iron deposition occured in mouse lung tissue of model group. The PCR array identified five ferroptosis-related genes that expression significantly decreased in model group compared with control group including carbonic anhydrase 9 (CA9), cysteinyl-tRNA synthetase 1 (CARS1), heat shock transcription factor 1 (HSF1), NADPH oxidase 3 (NOX3) and mitochondrial ferritin (FTMT)(P<0.05). GO functional enrichment analysis and KEGG pathway analysis showed that the DEGs were mainly related to temperature homeostasis, NADPH oxidase complex, and carbonate dehydratase activity, and were involved in nitrogen metabolism, aminoacyl-tRNA biosynthesis and legionellosis signaling pathways. RT-qPCR verification confirmed that the expression levels of CA9, CARS1, HSF1 and FTMT were significantly decreased in model group than those in control group (P<0.05). Conclusions Change of the expression of genes related to ferroptosis has been confirmed in a murine model of pulmonary fibrosis induced by bleomycin. The result indicates that ferroptosis is involved in the process of idiopathic pulmonary fibrosis, ferroptosis-associated DEGs might provide potential targets for clinical treatment of it.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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