Phenylbutyric acid inhibits epithelial-mesenchymal transition during bleomycin-induced lung fibrosis
| Autor: | De-Xiang Xu, Hui Zhao, Zhu-Xia Tan, Cheng Zhang, Lin-Feng Cao, Yuan-Hua Chen, Hou-Ying Qin |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Pathology medicine.medical_specialty Epithelial-Mesenchymal Transition Pulmonary Fibrosis Toxicology Bleomycin Endoplasmic Reticulum Protective Agents Collagen Type I Proinflammatory cytokine chemistry.chemical_compound Mice parasitic diseases Pulmonary fibrosis medicine Animals Epithelial–mesenchymal transition Sirius Red Lung urogenital system Chemistry Endoplasmic reticulum Transcription Factor RelA nutritional and metabolic diseases General Medicine medicine.disease Endoplasmic Reticulum Stress Phenylbutyrates Actins Collagen Type I alpha 1 Chain Disease Models Animal Cytoprotection Unfolded protein response Cancer research Unfolded Protein Response Female Chemical chaperone Signal Transduction |
| Zdroj: | Toxicology letters. 232(1) |
| ISSN: | 1879-3169 |
| Popis: | A recent report showed that unfolded protein response (UPR) signaling was activated during bleomycin (BLM)-induced pulmonary fibrosis. Phenylbutyric acid (PBA) is an endoplasmic reticulum (ER) chemical chaperone that inhibits the UPR signaling. The present study investigated the effects of PBA on BLM-induced epithelial-mesenchymal transition (EMT) and pulmonary fibrosis. For induction of pulmonary fibrosis, all mice except controls were intratracheally injected with a single dose of BLM (3.0mg/kg). In PBA+BLM group, mice were intraperitoneally injected with PBA (150mg/kg) daily. Three weeks after BLM injection, EMT was measured and pulmonary fibrosis was evaluated. BLM-induced pulmonary UPR activation was inhibited by PBA. Moreover, BLM-induced pulmonary nuclear factor kappa B (NF-κB) p65 activation was blocked by PBA. In addition, BLM-induced up-regulation of pulmonary inflammatory cytokines was repressed by PBA. Further analysis showed that BLM-induced α-smooth muscle actin (α-SMA), a marker for EMT, was significantly attenuated by PBA. Moreover, BLM-induced pulmonary collagen (Col1α1 and Col1α2) was obviously inhibited by PBA. Importantly, BLM-induced pulmonary fibrosis, as determined using Sirius red staining, was obviously alleviated by PBA. Taken together, these results suggest that PBA alleviates ER stress-mediated EMT in the pathogenesis of BLM-induced pulmonary fibrosis. |
| Databáze: | OpenAIRE |
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