Home
|
Inbox
|
Search
|
View Abstract
Role of Mitochondrial Antiviral Signaling Protein (MAVS) in the Pathogenesis of Bleomycin-Induced Pulmonary Fibrosis in Mice
Description
.abstract img { width:300px !important; height:auto; display:block; text-align:center; margin-top:10px } .abstract { overflow-x:scroll } .abstract table { width:100%; display:block; border:hidden; border-collapse: collapse; margin-top:10px } .abstract td, th { border-top: 1px solid #ddd; padding: 4px 8px; } .abstract tbody tr:nth-child(even) td { background-color: #efefef; } .abstract a { overflow-wrap: break-word; word-wrap: break-word; }
A7774 - Role of Mitochondrial Antiviral Signaling Protein (MAVS) in the Pathogenesis of Bleomycin-Induced Pulmonary Fibrosis in Mice
Author Block: J. Lee, S. Kim, C. Yoon, H. Shin, M. Kang; Yale Univ, New Haven, CT, United States.
RATIONALE: Mitochondria have emerged as important signaling organelles where intracellular signaling pathways are modulated to execute appropriate cellular functions. Mitochondrial antiviral signaling protein (MAVS) represents such an example to function as a platform molecule to mediate mitochondrial innate immune or inflammasomes signaling. The role of MAVS which plays in the pathogenesis of pulmonary fibrosis, however, has not been addressed yet.
METHODS: The tissue inflammatory and fibrotic remodeling responses, lung collagen contents and activation status of TGF-β signaling were evaluated and compared in lungs from bleomycin (1.5U/kg)-administered MAVS null mutant (-/-) and appropriate wild type (WT) controls.
RESULTS: Biochemical collagen assay and histologic evaluation revealed significant reduction of collagen deposition in lungs of MAVS-/- mice compared to those of WT controls after bleomycin treatment. Total cell recovery from bronchoalveolar lavage showed no statistical difference between two groups at 1, 2 and 3 weeks, respectively, after bleomycin treatment. Intriguingly, immunoblot evaluation revealed that bleomycin induced-phosphorylation of SMAD2 and SMAD3, important markers of TGF-β signaling activation, were significantly attenuated in lungs of MAVS-/- mice compared to those of WT controls. In addition, bleomycin induced-upregulation of fibronectin and alpha smooth muscle actin molecules were also significantly downregulated in lungs of MAVS-/- mice compared to those of WT controls. Importantly, immunohistochemistry evaluation demonstrated a strong induction of MAVS staining, especially in alveolar macrophages, after bleomycin administration.
CONCLUSION: MAVS, a key adaptor of mitochondrial innate immune signaling, may play an important role in the pathogenesis of bleomycin-induced pulmonary fibrosis.
Author Block: J. Lee, S. Kim, C. Yoon, H. Shin, M. Kang; Yale Univ, New Haven, CT, United States.
RATIONALE: Mitochondria have emerged as important signaling organelles where intracellular signaling pathways are modulated to execute appropriate cellular functions. Mitochondrial antiviral signaling protein (MAVS) represents such an example to function as a platform molecule to mediate mitochondrial innate immune or inflammasomes signaling. The role of MAVS which plays in the pathogenesis of pulmonary fibrosis, however, has not been addressed yet.
METHODS: The tissue inflammatory and fibrotic remodeling responses, lung collagen contents and activation status of TGF-β signaling were evaluated and compared in lungs from bleomycin (1.5U/kg)-administered MAVS null mutant (-/-) and appropriate wild type (WT) controls.
RESULTS: Biochemical collagen assay and histologic evaluation revealed significant reduction of collagen deposition in lungs of MAVS-/- mice compared to those of WT controls after bleomycin treatment. Total cell recovery from bronchoalveolar lavage showed no statistical difference between two groups at 1, 2 and 3 weeks, respectively, after bleomycin treatment. Intriguingly, immunoblot evaluation revealed that bleomycin induced-phosphorylation of SMAD2 and SMAD3, important markers of TGF-β signaling activation, were significantly attenuated in lungs of MAVS-/- mice compared to those of WT controls. In addition, bleomycin induced-upregulation of fibronectin and alpha smooth muscle actin molecules were also significantly downregulated in lungs of MAVS-/- mice compared to those of WT controls. Importantly, immunohistochemistry evaluation demonstrated a strong induction of MAVS staining, especially in alveolar macrophages, after bleomycin administration.
CONCLUSION: MAVS, a key adaptor of mitochondrial innate immune signaling, may play an important role in the pathogenesis of bleomycin-induced pulmonary fibrosis.
|
Home
|
Inbox
|
Search
|