Academic Journal
Bone Marrow CD11c+ Cell–Derived Amphiregulin Promotes Pulmonary Fibrosis
| العنوان: | Bone Marrow CD11c+ Cell–Derived Amphiregulin Promotes Pulmonary Fibrosis |
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| المؤلفون: | Ding, Lin, Liu, Tianju, Wu, Zhe, Hu, Biao, Nakashima, Taku, Ullenbruch, Matthew, Gonzalez De Los Santos, Francina, Phan, Sem H. |
| المصدر: | The Journal of Immunology ; volume 197, issue 1, page 303-312 ; ISSN 0022-1767 1550-6606 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2016 |
| الوصف: | Amphiregulin (AREG), an epidermal growth factor receptor ligand, is implicated in tissue repair and fibrosis, but its cellular source and role in regeneration versus fibrosis remain unclear. In this study, we hypothesize that AREG induced in bone marrow–derived CD11c+ cells is essential for pulmonary fibrosis. Thus, the objectives were to evaluate the importance and role of AREG in pulmonary fibrosis, identify the cellular source of AREG induction, and analyze its regulation of fibroblast function and activation. The results showed that lung AREG expression was significantly induced in bleomycin-induced pulmonary fibrosis. AREG deficiency in knockout mice significantly diminished pulmonary fibrosis. Analysis of AREG expression in major lung cell types revealed induction in fibrotic lungs predominantly occurred in CD11c+ cells. Moreover, depletion of bone marrow–derived CD11c+ cells suppressed both induction of lung AREG expression and pulmonary fibrosis. Conversely, adoptive transfer of bone marrow–derived CD11c+ cells from bleomycin-treated donor mice exacerbated pulmonary fibrosis, but not if the donor cells were made AREG deficient prior to transfer. CD11c+ cell-conditioned media or coculture stimulated fibroblast proliferation, activation, and myofibroblast differentiation in an AREG-dependent manner. Furthermore, recombinant AREG induced telomerase reverse transcriptase, which appeared to be essential for the proliferative effect. Finally, AREG significantly enhanced fibroblast motility, which was associated with increased expression of α6 integrin. These findings suggested that induced AREG specifically in recruited bone marrow–derived CD11c+ cells promoted bleomycin-induced pulmonary fibrosis by activation of fibroblast telomerase reverse transcriptase–dependent proliferation, motility, and indirectly, myofibroblast differentiation. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.4049/jimmunol.1502479 |
| الاتاحة: | https://doi.org/10.4049/jimmunol.1502479 https://journals.aai.org/jimmunol/article-pdf/197/1/303/1418540/1502479.pdf |
| رقم الانضمام: | edsbas.8F250D01 |
| قاعدة البيانات: | BASE |
| DOI: | 10.4049/jimmunol.1502479 |
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