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Distinct Patterns of Wnt3a and Wnt5a Signaling Pathway in the Lung from Rats with Endotoxic Shock.

Hii HP, Liao MH, Chen SJ, Wu CC, Shih CC - PLoS ONE (2015)

Bottom Line: Wnt3a signaling has been implicated in anti-inflammatory effects, whereas Wnt5a signaling has been postulated to have pro-inflammatory properties.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.These findings indicate the major components of Wnt3a and Wnt5a signaling in the lung are disturbed under endotoxic insult.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Chi Mei Medical Center, Tainan, R.O.C., Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus

Changes of lung (A) superoxide production and (B) water accumulation in rats treated with lipopolysaccharide (LPS).Depicted are changes in superoxide production and water accumulation at the end of experiment (at 6 h) in rats that received saline (Control; 0.9% NaCl, i.v., n = 7) or LPS (10 mg/kg, i.v., n = 7). Data expressed as mean ± SEM. *P < 0.05, LPS vs. Control. (C) Polymorphonuclear neutrophil (PMN) infiltration index and (D) representative histopathologic features of lung tissue sections obtained from rats treated with LPS. Depiction of the changes in PMN infiltration index at the end of experiment (at 6 h) in different groups of animals which received saline (Control, 0.9% NaCl, i.v., n = 3) or LPS (10 mg/kg, i.v., n = 3). Data expressed as mean ± SEM. *P < 0.05, LPS vs. Control. Light microscopy showed lung sections of rats in Control and LPS group. Arrows represent neutrophil infiltration and interstitial edema. Original magnification x 400.
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pone.0134492.g003: Changes of lung (A) superoxide production and (B) water accumulation in rats treated with lipopolysaccharide (LPS).Depicted are changes in superoxide production and water accumulation at the end of experiment (at 6 h) in rats that received saline (Control; 0.9% NaCl, i.v., n = 7) or LPS (10 mg/kg, i.v., n = 7). Data expressed as mean ± SEM. *P < 0.05, LPS vs. Control. (C) Polymorphonuclear neutrophil (PMN) infiltration index and (D) representative histopathologic features of lung tissue sections obtained from rats treated with LPS. Depiction of the changes in PMN infiltration index at the end of experiment (at 6 h) in different groups of animals which received saline (Control, 0.9% NaCl, i.v., n = 3) or LPS (10 mg/kg, i.v., n = 3). Data expressed as mean ± SEM. *P < 0.05, LPS vs. Control. Light microscopy showed lung sections of rats in Control and LPS group. Arrows represent neutrophil infiltration and interstitial edema. Original magnification x 400.

Mentions: To investigate the degrees of lung inflammation and edema in LPS-induced endotoxemia animals, we measured the levels of superoxide production, water accumulation and neutrophil infiltration in the lung. The lung from rats with endotoxic shock revealed significant increases in superoxide level and water accumulation when compared with the lung from Control group at 6h after LPS treatment (Fig 3A and 3B). In addition, LPS led to marked interstitial edema and overt neutrophil infiltration in the lung at the end of the experiment (Fig 3C and 3D). Thus, the injection of LPS caused significant inflammation and edema in the lung of rats with endotoxic shock.


Distinct Patterns of Wnt3a and Wnt5a Signaling Pathway in the Lung from Rats with Endotoxic Shock.

Hii HP, Liao MH, Chen SJ, Wu CC, Shih CC - PLoS ONE (2015)

Changes of lung (A) superoxide production and (B) water accumulation in rats treated with lipopolysaccharide (LPS).Depicted are changes in superoxide production and water accumulation at the end of experiment (at 6 h) in rats that received saline (Control; 0.9% NaCl, i.v., n = 7) or LPS (10 mg/kg, i.v., n = 7). Data expressed as mean ± SEM. *P < 0.05, LPS vs. Control. (C) Polymorphonuclear neutrophil (PMN) infiltration index and (D) representative histopathologic features of lung tissue sections obtained from rats treated with LPS. Depiction of the changes in PMN infiltration index at the end of experiment (at 6 h) in different groups of animals which received saline (Control, 0.9% NaCl, i.v., n = 3) or LPS (10 mg/kg, i.v., n = 3). Data expressed as mean ± SEM. *P < 0.05, LPS vs. Control. Light microscopy showed lung sections of rats in Control and LPS group. Arrows represent neutrophil infiltration and interstitial edema. Original magnification x 400.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4517818&req=5

pone.0134492.g003: Changes of lung (A) superoxide production and (B) water accumulation in rats treated with lipopolysaccharide (LPS).Depicted are changes in superoxide production and water accumulation at the end of experiment (at 6 h) in rats that received saline (Control; 0.9% NaCl, i.v., n = 7) or LPS (10 mg/kg, i.v., n = 7). Data expressed as mean ± SEM. *P < 0.05, LPS vs. Control. (C) Polymorphonuclear neutrophil (PMN) infiltration index and (D) representative histopathologic features of lung tissue sections obtained from rats treated with LPS. Depiction of the changes in PMN infiltration index at the end of experiment (at 6 h) in different groups of animals which received saline (Control, 0.9% NaCl, i.v., n = 3) or LPS (10 mg/kg, i.v., n = 3). Data expressed as mean ± SEM. *P < 0.05, LPS vs. Control. Light microscopy showed lung sections of rats in Control and LPS group. Arrows represent neutrophil infiltration and interstitial edema. Original magnification x 400.
Mentions: To investigate the degrees of lung inflammation and edema in LPS-induced endotoxemia animals, we measured the levels of superoxide production, water accumulation and neutrophil infiltration in the lung. The lung from rats with endotoxic shock revealed significant increases in superoxide level and water accumulation when compared with the lung from Control group at 6h after LPS treatment (Fig 3A and 3B). In addition, LPS led to marked interstitial edema and overt neutrophil infiltration in the lung at the end of the experiment (Fig 3C and 3D). Thus, the injection of LPS caused significant inflammation and edema in the lung of rats with endotoxic shock.

Bottom Line: Wnt3a signaling has been implicated in anti-inflammatory effects, whereas Wnt5a signaling has been postulated to have pro-inflammatory properties.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.These findings indicate the major components of Wnt3a and Wnt5a signaling in the lung are disturbed under endotoxic insult.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Chi Mei Medical Center, Tainan, R.O.C., Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus