Dataset Information

Keratinocyte Growth Factor-2 Reduces Inflammatory Response to Acute Lung Injury Induced by Oleic Acid in Rats by Regulating Key Proteins of the Wnt/?-Catenin Signaling Pathway.

ABSTRACT: Reducing inflammation can effectively relieve acute lung injury (ALI). Objective. To test whether keratinocyte growth factor-2 (KGF-2) can reduce oleic acid-induced inflammation in ALI of rats and explore its possible mechanism. Methods. 45 Sprague-Dawley rats were randomly divided into control group, ALI group, and ALI?+?KGF-2 group. The animal model of acute lung injury was established by injecting 0.1?mL/kg oleic acid into the tail vein of rats. Rats in the control group were injected with equal volume of normal saline (NS). Each group needs pretreatment 72 hours before the preparation of the acute lung injury model. The control group and ALI group were instilled with 5?ml/kg NS through the airway, and the same amount of KGF-2 was instilled in the ALI?+?KGF-2 group. It takes 8 hours to successfully prepare the ALI model. Observe the pathological changes of lung tissue through light microscopy, ultrastructural changes through electron microscopy, and the lung wettability/dry weight (w/d) ratio and lung permeability index (LPI). By detecting changes in inflammatory factors in lung tissue and changes in the number of BALF cells, the changes in inflammation in each group were observed. The expressions of Wnt5a, ?-catenin, and APC in lung tissue were detected by immunohistochemistry and Western blot. The changes of key proteins in Wnt/?-catenin signaling pathway in the lung tissue of each group were observed. Result. Compared with the ALI group, after KGF-2 pretreatment, the degree of lung injury was reduced, the expression of inflammatory factors was reduced, and the number of red blood cells and white blood cells in BALF was reduced. It can also be observed that the expression of Wnt5a, ?-catenin, and APC, a key protein in the Wnt/?-catenin signaling pathway, is reduced. The analysis showed that the number of inflammatory factors, red blood cells, and white blood cells in BALF was positively correlated with the expression of Wnt5a, ?-catenin, and APC. Conclusion. KGF-2 may reduce the inflammatory response in ALI induced by oleic acid by regulating key proteins in the Wnt/?-catenin signaling pathway.

SUBMITTER: Tenghao S

PROVIDER: S-EPMC7322598 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Keratinocyte Growth Factor-2 Reduces Inflammatory Response to Acute Lung Injury Induced by Oleic Acid in Rats by Regulating Key Proteins of the Wnt/β-Catenin Signaling Pathway.

Tenghao Shao S Ning Chen C Shenghai Wang W Qinlong Sun S Jiaqian Wu W Kuo Wang W Zhanbiao Yu Y Xigang Ma M

Evidence-based complementary and alternative medicine : eCAM 20200620

Reducing inflammation can effectively relieve acute lung injury (ALI). Objective. To test whether keratinocyte growth factor-2 (KGF-2) can reduce oleic acid-induced inflammation in ALI of rats and explore its possible mechanism. Methods. 45 Sprague-Dawley rats were randomly divided into control group, ALI group, and ALI + KGF-2 group. The animal model of acute lung injury was established by injecting 0.1 mL/kg oleic acid into the tail vein of rats. Rats in the control group were in ...[more]

PMID: 32655669

Similar Datasets

Project description:ObjectiveThe aim of this study was to examine the role of keratinocyte growth factor-2 (KGF-2) in oleic acid-induced acute lung injury (ALI) in rats.Methods Forty-five healthy adult male Sprague Dawley rats were divided into 3 groups. Rat ALI model was established by injection of 0.01 mL/kg oleic acid into the tail vein. Rats in the control group were injected with the same amount of normal saline (NS). In the ALI + KGF-2 group, 5 mg/kg of KGF-2 was instilled into the airway of rats 72 hours before the model preparation, and the control group and the ALI model group were instilled with the same amount of NS. The lung permeability index (LPI) and lung wet/dry weight (W / D) ratios were measured 8 hours after the model preparation. The permeability of pulmonary microvascular endothelium was evaluated by Evans blue leakage test. Histopathological changes were observed under light microscope and the ALI pathology score (LIS) was calculated. Ultrastructural changes of lung tissue were observed under electron microscope. The apoptosis was detected by TUNEL assay. The expression of Claudin-5, ZO-1, and VE Cadherin in lung tissue was qualitatively and quantitatively analyzed by immunohistochemistry, Western Blot, and qRT-PCR, respectively.ResultsThe ALI model group had severe lung injury and obvious pathological changes, including alveolar septal thickening and inflammatory cell infiltration. TUNEL assay showed that the apoptosis of ALI group was significantly increased. The LIS score, lung W/D ratio, LPI, and Evans blue leakage were significantly higher than those in the control group; electron microscopy showed that the alveolar-capillary barrier was severely damaged in the ALI group. Compared with the control group, the expression of Claudin-5, ZO-1, and VE cadherin in the lung tissue of the ALI model group was significantly attenuated. After pretreatment with KGF-2, the degree of lung tissue damage was significantly reduced and the pathological changes were significantly improved. TUNEL assay showed that the apoptosis of ALI group was decreased. Lung W/D ratio, LPI, and Evans blue leakage decreased; electron microscopy showed that the alveolar-capillary barrier of ALI group recovered significantly. Compared with the ALI model group, the expression of Claudin-5, ZO-1, and VE cadherin in the lung tissue of the KGF-2 pretreatment group increased.ConclusionThe results indicate that KGF-2 may attenuate oleic acid-induced ALI in rats by maintaining the pulmonary microvascular endothelial barrier, which is an effective ALI preventive measure.

Project description:Traumatic CNS injury triggers a systemic inflammatory response syndrome (SIRS), in which circulating inflammatory cells invade body organs causing local inflammation and tissue damage. We have shown that the SIRS caused by spinal cord injury is greatly reduced by acute intravenous treatment with an antibody against the CD11d subunit of the CD11d/CD18 integrin expressed by neutrophils and monocyte/macrophages, a treatment that reduces their efflux from the circulation. Traumatic brain injury (TBI) is a frequently occurring injury after motor vehicle accidents, sporting and military injuries, and falls. Our studies have shown that the anti-CD11d treatment diminishes brain inflammation and oxidative injury after moderate or mild TBI, improving neurological outcomes. Accordingly, we examined the impact of this treatment on the SIRS triggered by TBI. The anti-CD11d treatment was given at 2h after a single moderate (2.5-3.0 atm) or 2 and 24h after each of three consecutive mild (1.0-1.5 atm) fluid percussion TBIs. Sham-injured, saline-treated rats served as controls. At 24h, 72 h, and 4 or 8 weeks after the single TBI and after the third of three TBIs, lungs of rats were examined histochemically, immunocytochemically and biochemically for downstream effects of SIRS including inflammation, tissue damage and expression of oxidative enzymes. Lung sections revealed that both the single moderate and repeated mild TBI caused alveolar disruption, thickening of inter-alveolar tissue, hemorrhage into the parenchyma and increased density of intra-and peri-alveolar macrophages. The anti-CD11d treatment decreased the intrapulmonary influx of neutrophils and the density of activated macrophages and the activity of myeloperoxidase after these TBIs. Moreover, Western blotting studies showed that the treatment decreased lung protein levels of oxidative enzymes gp91(phox), inducible nitric oxide synthase and cyclooxygenase-2, as well as the apoptotic pathway enzyme caspase-3 and levels of 4-hydroxynonenal-bound proteins (an indicator of lipid peroxidation). Decreased expression of the cytoprotective transcription factor Nrf2 reflected decreased lung oxidative stress. Anti-CD11d treatment also diminished the lung concentration of free radicals and tissue aldehydes. In conclusion, the substantial lung component of the SIRS after single or repeated TBIs is significantly decreased by a simple, minimally invasive and short-lasting anti-inflammatory treatment.

Dataset Information

Keratinocyte Growth Factor-2 Reduces Inflammatory Response to Acute Lung Injury Induced by Oleic Acid in Rats by Regulating Key Proteins of the Wnt/?-Catenin Signaling Pathway.

Publications

Keratinocyte Growth Factor-2 Reduces Inflammatory Response to Acute Lung Injury Induced by Oleic Acid in Rats by Regulating Key Proteins of the Wnt/<i>β</i>-Catenin Signaling Pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets