Academic Journal
Caveolin-1 scaffolding domain peptide abrogates autophagy dysregulation in pulmonary fibrosis
| العنوان: | Caveolin-1 scaffolding domain peptide abrogates autophagy dysregulation in pulmonary fibrosis |
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| المؤلفون: | Shalini Venkatesan, Liang Fan, Hua Tang, Nagarjun V. Konduru, Sreerama Shetty |
| المصدر: | Scientific Reports, Vol 12, Iss 1, Pp 1-10 (2022) |
| بيانات النشر: | Nature Portfolio, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | Abstract Idiopathic pulmonary fibrosis (IPF) is the most common and fatal form of interstitial lung disease. IPF is characterized by irreversible scarring of the lungs leading to lung function decline. Although the etiology remains poorly understood, dysregulated autophagy in alveolar-epithelial cells (AECs) together with interplay between apoptotic-AECs and proliferative-myofibroblasts have been strongly implicated in IPF pathogenesis. Recent studies have revealed that a caveolin-1-derived 7-mer peptide, CSP7, mitigates established PF at least in part by improving AEC viability. In the present study, we aimed to determine whether and how CSP7 regulates autophagy in fibrotic-lung AECs. We found that p53 and autophagic proteins were markedly upregulated in AECs from mice with single/multi-doses of bleomycin—or silica-induced PF. This was abolished following treatment of PF-mice with CSP7. Further, CSP7 abrogated silica- or bleomycin-induced p53 and autophagy proteins in AECs. Immunoprecipitation further revealed that CSP7 abolishes the interaction of caveolin-1 with LC3BII and p62 in AECs. AEC-specific p53-knockout mice resisted silica- or bleomycin-induced changes in autophagy proteins, or CSP7 treatment. Our findings provide a novel mechanism by which CSP7 inhibits dysregulated autophagy in injured AECs and mitigates existing PF. These results affirm the potential of CSP7 for treating established PF, including IPF and silicosis. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-022-14832-4 |
| URL الوصول: | https://doaj.org/article/35392963ff254b65b4e807f7141433c3 |
| رقم الانضمام: | edsdoj.35392963ff254b65b4e807f7141433c3 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-022-14832-4 |