دورية أكاديمية
Role of lung ornithine aminotransferase in idiopathic pulmonary fibrosis: regulation of mitochondrial ROS generation and TGF-β1 activity
| العنوان: | Role of lung ornithine aminotransferase in idiopathic pulmonary fibrosis: regulation of mitochondrial ROS generation and TGF-β1 activity |
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| المؤلفون: | Jong-Uk Lee, Ki Sung Song, Jisu Hong, Hyesun Shin, Eunji Park, Junyeong Baek, Shinhee Park, Ae-Rin Baek, Junehyuk Lee, An Soo Jang, Do Jin Kim, Su Sie Chin, U-Jin Kim, Sung Hwan Jeong, Sung-Woo Park |
| المصدر: | Experimental and Molecular Medicine, Vol 56, Iss 2, Pp 478-490 (2024) |
| بيانات النشر: | Nature Publishing Group, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine LCC:Biochemistry |
| مصطلحات موضوعية: | Medicine, Biochemistry, QD415-436 |
| الوصف: | Abstract Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant lung remodeling and the excessive accumulation of extracellular matrix (ECM) proteins. In a previous study, we found that the levels of ornithine aminotransferase (OAT), a principal enzyme in the proline metabolism pathway, were increased in the lungs of patients with IPF. However, the precise role played by OAT in the pathogenesis of IPF is not yet clear. The mechanism by which OAT affects fibrogenesis was assessed in vitro using OAT-overexpressing and OAT-knockdown lung fibroblasts. The therapeutic effects of OAT inhibition were assessed in the lungs of bleomycin-treated mice. OAT expression was increased in fibrotic areas, principally in interstitial fibroblasts, of lungs affected by IPF. OAT levels in the bronchoalveolar lavage fluid of IPF patients were inversely correlated with lung function. The survival rate was significantly lower in the group with an OAT level >75.659 ng/mL than in the group with an OAT level ≤75.659 ng/mL (HR, 29.53; p = 0.0008). OAT overexpression and knockdown increased and decreased ECM component production by lung fibroblasts, respectively. OAT knockdown also inhibited transforming growth factor-β1 (TGF)-β1 activity and TGF-β1 pathway signaling. OAT overexpression increased the generation of mitochondrial reactive oxygen species (ROS) by activating proline dehydrogenase. The OAT inhibitor L-canaline significantly attenuated bleomycin-induced lung injury and fibrosis. In conclusion, increased OAT levels in lungs affected by IPF contribute to the progression of fibrosis by promoting excessive mitochondrial ROS production, which in turn activates TGF-β1 signaling. OAT may be a useful target for treating patients with fibrotic lung diseases, including IPF. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2092-6413 |
| العلاقة: | https://doaj.org/toc/2092-6413Test |
| DOI: | 10.1038/s12276-024-01170-w |
| الوصول الحر: | https://doaj.org/article/af5e4a708dc342ef9ec9cdffe61294e4Test |
| رقم الانضمام: | edsdoj.f5e4a708dc342ef9ec9cdffe61294e4 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20926413 |
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| DOI: | 10.1038/s12276-024-01170-w |