Melatonin Inhibits Endoplasmic Reticulum Stress and Epithelial-Mesenchymal Transition during Bleomycin-Induced Pulmonary Fibrosis in Mice
| Autor: | Hou-Ying Qing, Qing-Qing Wu, Yuan-Hua Chen, Lin-Feng Cao, Hua Wang, Hui Zhao, De-Xiang Xu, Rong-Ru Liu, Cheng Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
endocrine system congenital hereditary and neonatal diseases and abnormalities Pulmonary Fibrosis Respiratory System lcsh:Medicine Biology Bleomycin Biochemistry Melatonin chemistry.chemical_compound Fibrosis Internal medicine Pulmonary fibrosis medicine Epithelial–mesenchymal transition lcsh:Science Sirius Red Cellular Stress Responses Multidisciplinary urogenital system Endoplasmic reticulum lcsh:R nutritional and metabolic diseases Biology and Life Sciences Cell Biology medicine.disease Hormones Endocrinology chemistry Cell Processes Endoplasmic Reticulum Stress Response Unfolded protein response lcsh:Q Anatomy Lungs hormones hormone substitutes and hormone antagonists medicine.drug Research Article Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 9, Iss 5, p e97266 (2014) |
| ISSN: | 1932-6203 |
| Popis: | Several reports indicate that melatonin alleviates bleomycin (BLM)-induced pulmonary fibrosis in rodent animals. Nevertheless, the exact mechanism remains obscure. The present study investigated the effects of melatonin on endoplasmic reticulum (ER) stress and epithelial-mesenchymal transition (EMT) during BLM-induced lung fibrosis. For the induction of pulmonary fibrosis, mice were intratracheally injected with a single dose of BLM (5.0 mg/kg). Some mice were intraperitoneally injected with melatonin (5 mg/kg) daily for a period of 3 wk. Twenty-one days after BLM injection, lung fibrosis was evaluated. As expected, melatonin significantly alleviated BLM-induced pulmonary fibrosis, as evidenced by Sirius red staining. Moreover, melatonin significantly attenuated BLM-induced EMT to myofibroblasts, as determined by its repression of α-SMA expression. Further analysis showed that melatonin markedly attenuated BLM-induced GRP78 up-regulation and elevation of the cleaved ATF6 in the lungs. Moreover, melatonin obviously attenuated BLM-induced activation of pulmonary eIF2α, a downstream target of the PERK pathway. Finally, melatonin repressed BLM-induced pulmonary IRE1α phosphorylation. Correspondingly, melatonin inhibited BLM-induced activation of XBP-1 and JNK, two downstream targets of the IRE1 pathway. Taken together, these results suggest that melatonin alleviates ER stress and ER stress-mediated EMT in the process of BLM-induced pulmonary fibrosis. |
| Databáze: | OpenAIRE |
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