title: Early activation of pulmonary TGF-β1/Smad2 signaling in mice with acute pancreatitis-associated acute lung injury.
abstract: 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.
authors.affiliation: Department of Surgery, Clinical Sciences-Lund, Lund University and Skåne University Hospital, 221 85 Lund, Sweden.
authors.forename: Hamid
authors.identifier: 0000-0001-7748-286X
authors.initials: H
authors.lastname: Akbarshahi
authors.affiliation: Department of Surgery, Clinical Sciences-Lund, Lund University and Skåne University Hospital, 221 85 Lund, Sweden.
authors.forename: Asha
authors.initials: A
authors.lastname: Sam
authors.affiliation: Department of Surgery, Clinical Sciences-Lund, Lund University and Skåne University Hospital, 221 85 Lund, Sweden ; The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Chaolei
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Surgery, Clinical Sciences-Lund, Lund University and Skåne University Hospital, 221 85 Lund, Sweden ; Department of Oncology, Clinical Sciences-Lund, Skåne University Hospital and Lund University, 221 85 Lund, Sweden.
authors.forename: Ann H
authors.initials: AH
authors.lastname: Rosendahl
authors.affiliation: Department of Surgery, Clinical Sciences-Lund, Lund University and Skåne University Hospital, 221 85 Lund, Sweden.
authors.forename: Roland
authors.identifier: 0000-0003-0778-8630
authors.initials: R
authors.lastname: Andersson
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010195:Pancreatitis / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625842:Tgfbr1 protein, mouse