Early Activation of Pulmonary TGF-β1/Smad2 Signaling in Mice with Acute Pancreatitis-Associated Acute Lung Injury

Acute lung injury is caused by many factors including acute pancreatitis. There is no specific therapy directed at underlying pathophysiological mechanisms for acute lung injury. Transforming growth factor-β (TGF-β) is involved in the resolution of lung injury in later phases of the disease. Some ev...

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Main Authors: Hamid Akbarshahi, Asha Sam, Chaolei Chen, Ann H. Rosendahl, Roland Andersson
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2014/148029
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author Hamid Akbarshahi
Asha Sam
Chaolei Chen
Ann H. Rosendahl
Roland Andersson
author_facet Hamid Akbarshahi
Asha Sam
Chaolei Chen
Ann H. Rosendahl
Roland Andersson
author_sort Hamid Akbarshahi
collection DOAJ
description Acute lung injury is caused by many factors including acute pancreatitis. There is no specific therapy directed at underlying pathophysiological mechanisms for acute lung injury. Transforming growth factor-β (TGF-β) is involved in the resolution of lung injury in later phases of the disease. Some evidence exists demonstrating that TGF-β not only is involved in the late stages, but also contributes to lung injury early on in the progress of the disease. Acute pancreatitis was induced using ductal ligation in mice. TGF-β1, 2, and 3, TβRII, ALK-5, Smad2, 3, 4, and 7, and P-Smad2 expression in the lungs were analyzed at 9 and 24 h. We demonstrate that TGF-β1 levels in the lungs of mice with acute pancreatitis increase as early as 9 h after induction. We observed an increased expression of ALK-5 in acute pancreatitis at both 9 and 24 h. Inhibitory Smad7 expression was transiently increased at 9 h in acute pancreatitis, but reduced later at 24 h, with a concomitant increased nuclear translocation of phosphorylated Smad2. Our findings demonstrate activation of TGF-β signaling in the lungs as early as 24 h after acute pancreatitis, suggesting that TGF-β may represent a potential therapeutic candidate in acute pancreatitis-induced acute lung injury.
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spelling doaj-art-38a599ff3dca411a95c1f5d1bf4ab6eb2025-02-03T01:02:02ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/148029148029Early Activation of Pulmonary TGF-β1/Smad2 Signaling in Mice with Acute Pancreatitis-Associated Acute Lung InjuryHamid Akbarshahi0Asha Sam1Chaolei Chen2Ann H. Rosendahl3Roland Andersson4Department of Surgery, Clinical Sciences-Lund, Lund University and Skåne University Hospital, 221 85 Lund, SwedenDepartment of Surgery, Clinical Sciences-Lund, Lund University and Skåne University Hospital, 221 85 Lund, SwedenDepartment of Surgery, Clinical Sciences-Lund, Lund University and Skåne University Hospital, 221 85 Lund, SwedenDepartment of Surgery, Clinical Sciences-Lund, Lund University and Skåne University Hospital, 221 85 Lund, SwedenDepartment of Surgery, Clinical Sciences-Lund, Lund University and Skåne University Hospital, 221 85 Lund, SwedenAcute lung injury is caused by many factors including acute pancreatitis. There is no specific therapy directed at underlying pathophysiological mechanisms for acute lung injury. Transforming growth factor-β (TGF-β) is involved in the resolution of lung injury in later phases of the disease. Some evidence exists demonstrating that TGF-β not only is involved in the late stages, but also contributes to lung injury early on in the progress of the disease. Acute pancreatitis was induced using ductal ligation in mice. TGF-β1, 2, and 3, TβRII, ALK-5, Smad2, 3, 4, and 7, and P-Smad2 expression in the lungs were analyzed at 9 and 24 h. We demonstrate that TGF-β1 levels in the lungs of mice with acute pancreatitis increase as early as 9 h after induction. We observed an increased expression of ALK-5 in acute pancreatitis at both 9 and 24 h. Inhibitory Smad7 expression was transiently increased at 9 h in acute pancreatitis, but reduced later at 24 h, with a concomitant increased nuclear translocation of phosphorylated Smad2. Our findings demonstrate activation of TGF-β signaling in the lungs as early as 24 h after acute pancreatitis, suggesting that TGF-β may represent a potential therapeutic candidate in acute pancreatitis-induced acute lung injury.http://dx.doi.org/10.1155/2014/148029
spellingShingle Hamid Akbarshahi
Asha Sam
Chaolei Chen
Ann H. Rosendahl
Roland Andersson
Early Activation of Pulmonary TGF-β1/Smad2 Signaling in Mice with Acute Pancreatitis-Associated Acute Lung Injury
Mediators of Inflammation
title Early Activation of Pulmonary TGF-β1/Smad2 Signaling in Mice with Acute Pancreatitis-Associated Acute Lung Injury
title_full Early Activation of Pulmonary TGF-β1/Smad2 Signaling in Mice with Acute Pancreatitis-Associated Acute Lung Injury
title_fullStr Early Activation of Pulmonary TGF-β1/Smad2 Signaling in Mice with Acute Pancreatitis-Associated Acute Lung Injury
title_full_unstemmed Early Activation of Pulmonary TGF-β1/Smad2 Signaling in Mice with Acute Pancreatitis-Associated Acute Lung Injury
title_short Early Activation of Pulmonary TGF-β1/Smad2 Signaling in Mice with Acute Pancreatitis-Associated Acute Lung Injury
title_sort early activation of pulmonary tgf β1 smad2 signaling in mice with acute pancreatitis associated acute lung injury
url http://dx.doi.org/10.1155/2014/148029
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