Home
|
Inbox
|
Search
|
View Abstract
Endothelial Mir92a-KLF Signaling in Acute Lung Injury
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; }
A2249 - Endothelial Mir92a-KLF Signaling in Acute Lung Injury
Author Block: Y. Fang1, R. Huang1, D. Wu1, O. Myung-Jin1, A. Y. Meliton1, M. Tirrell2, G. M. Mutlu1; 1Medicine, The University of Chicago, Chicago, IL, United States, 2Institute for Molecular Engineering, The University of Chicago, Chicago, IL, United States.
Introduction: Acute respiratory distress syndrome (ARDS) is caused by widespread endothelial barrier disruption and uncontrolled cytokine storm. Our recent studies using animal and in vitro models demonstrated that disruption of endothelial transcription factor Kruppel-like factor 2 (KLF2) results in dysregulation of lung microvascular homeostasis and contributes to lung pathology in ARDS. However, the upstream regulators leading to KLF2 inhibition during acute injury remain poorly understood. Methods: Animal and in vitro models of acute lung injury were used to investigate putative upstream regulators of endothelial KLF2. We identified that microRNA-92a (miR-92a) as a key negative regulator of KLF2 expression in pulmonary microvascular endothelium. Intratracheal delivery of LPS significantly increases miR-92a expression in mouse lungs leading to KLF2 suppression. Nanoparticles were engineered to inhibit miR-92a and restore KLF2 expression in mouse models of ARDS. Conclusions: Increased miR-92a and reduced KLF2 causatively lead to acute lung injury. Nanomedicine has unique potential to manipulate miR92a-KLF2 signaling during ARDS.
Author Block: Y. Fang1, R. Huang1, D. Wu1, O. Myung-Jin1, A. Y. Meliton1, M. Tirrell2, G. M. Mutlu1; 1Medicine, The University of Chicago, Chicago, IL, United States, 2Institute for Molecular Engineering, The University of Chicago, Chicago, IL, United States.
Introduction: Acute respiratory distress syndrome (ARDS) is caused by widespread endothelial barrier disruption and uncontrolled cytokine storm. Our recent studies using animal and in vitro models demonstrated that disruption of endothelial transcription factor Kruppel-like factor 2 (KLF2) results in dysregulation of lung microvascular homeostasis and contributes to lung pathology in ARDS. However, the upstream regulators leading to KLF2 inhibition during acute injury remain poorly understood. Methods: Animal and in vitro models of acute lung injury were used to investigate putative upstream regulators of endothelial KLF2. We identified that microRNA-92a (miR-92a) as a key negative regulator of KLF2 expression in pulmonary microvascular endothelium. Intratracheal delivery of LPS significantly increases miR-92a expression in mouse lungs leading to KLF2 suppression. Nanoparticles were engineered to inhibit miR-92a and restore KLF2 expression in mouse models of ARDS. Conclusions: Increased miR-92a and reduced KLF2 causatively lead to acute lung injury. Nanomedicine has unique potential to manipulate miR92a-KLF2 signaling during ARDS.
|
Home
|
Inbox
|
Search
|