title: Distinct Patterns of Wnt3a and Wnt5a Signaling Pathway in the Lung from Rats with Endotoxic Shock.
abstract: Septic shock is a syndrome with severe hypotension and multiple organ dysfunction caused by an imbalance between pro-inflammatory and anti-inflammatory response. The most common risk factor of acute lung injury is severe sepsis. Patients with sepsis-related acute respiratory distress syndrome have higher mortality. Recent studies reveal regulatory roles of Wnt3a and Wnt5a signaling in inflammatory processes. Wnt3a signaling has been implicated in anti-inflammatory effects, whereas Wnt5a signaling has been postulated to have pro-inflammatory properties. However, the balance between Wnt3a and Wnt5a signaling pathway in the lung of rats with endotoxic shock has not been determined. Thus, we investigated the major components of Wnt3a and Wnt5a signaling pathway in the lung of endotoxemic rats. Male Wistar rats were intravenously infused with saline or lipopolysaccharide (LPS, 10 mg/kg). The changes of hemodynamics, biochemical variables, and arterial blood gas were examined during the experimental period. At 6 h after saline or LPS, animals were sacrificed, and lungs were obtained for analyzing superoxide production, water accumulation, histologic assessment, and protein expressions of Wnt3a and Wnt5a signaling pathway. Animals that received LPS showed circulatory failure, multiple organ dysfunction, metabolic acidosis, hyperventilation, lung edema, and high mortality. The lung from rats with endotoxic shock exhibited significant decreases in the levels of Wnt3a, Fzd1, Dsh1, phosphorylated GSK-3β at Ser9, and β-catenin. In contrast, the expressions of Wnt5a, Fzd5, and CaMKII were up-regulated in the lung of endotoxemic rats. These findings indicate the major components of Wnt3a and Wnt5a signaling in the lung are disturbed under endotoxic insult.
authors.affiliation: Department of Surgery, Chi Mei Medical Center, Tainan, R.O.C., Taiwan.
authors.forename: Hiong-Ping
authors.initials: HP
authors.lastname: Hii
authors.affiliation: Department of Pharmacology, National Defense Medical Center, Taipei, R.O.C., Taiwan.
authors.forename: Mei-Hui
authors.initials: MH
authors.lastname: Liao
authors.affiliation: Department of Nursing, Kang-Ning Junior College of Medical Care and Management, Taipei, R.O.C., Taiwan; Department of Physiology, National Defense Medical Center, Taipei, R.O.C., Taiwan.
authors.forename: Shiu-Jen
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, National Defense Medical Center, Taipei, R.O.C., Taiwan.
authors.forename: Chin-Chen
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, National Defense Medical Center, Taipei, R.O.C., Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, R.O.C., Taiwan.
authors.forename: Chih-Chin
authors.initials: CC
authors.lastname: Shih
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D004731:Endotoxins / Q000633:toxicity; D006439:Hemodynamics; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D000071818:Wnt-5a Protein; D060509:Wnt3A Protein / Q000378:metabolism*
chemical_list: D004731:Endotoxins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D060509:Wnt3A Protein; C491837:Wnt5a protein, rat; D013481:Superoxides