OSI-027 alleviates rapamycin insensitivity by modulation of mTORC2/AKT/TGF-β1 and mTORC1/4E-BP1 signaling in hyperoxia-induced lung injury infant rats

2021 ◽  
Author(s):  
Li Long ◽  
Mulin Liang ◽  
Yanling Liu ◽  
Pan Wang ◽  
Hongxing Dang
Keyword(s):  
Lung Injury ◽  
Infant Rats ◽  
Tgf Β1

scholarly journals microRNA-145-5p attenuates acute lung injury via targeting ETS2

2021 ◽  
Author(s):  
Liang Qiao ◽  
Rongxia Li ◽  
Shangang Hu ◽  
Yu Liu ◽  
Hongqiang Liu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Growth Factor ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Transforming Growth Factor ◽  
Recombinant Adenovirus ◽  
Transforming Growth Factor Β1 ◽  
Inflammatory Factors ◽  
Smad Pathway ◽  
Tgf Β1

Abstract Objective Previously, the protective effect of microRNA (miR)-145-5p has been discovered in acute lung injury (ALI). Thus, this study attempts to further discuss the mechanism of miR-145-5p in ALI through the downstream E26 transformation-specific proto-oncogene 2 (ETS2)/transforming growth factor β1 (TGF-β1)/Smad pathway. Methods A lipopolysaccharide (LPS)-induced rat ALI model was established. Recombinant adenovirus miR-145-5p and/or ETS2 overexpression plasmid was administrated into rats. Afterwards, pathological damage in the lung tissue, wet/dry (W/D) ratio, apoptosis and contents of serum inflammatory factors were observed. miR-145-5p, ETS2, TGF-β1, Smad2/3, phosphorylated Smad2/3 levels were measured in rats. Results miR-145-5p was down-regulated, ETS2 was up-regulated and TGF-β1/Smad pathway was activated in LPS-suffered rats. Overexpression of miR-145-5p inactivated the TGF-β1/Smad pathway and attenuated ALI, as reflected by relived pathological damage, and decreased W/D ratio, apoptosis and inflammatory response. Oppositely, loss of miR-145-5p or enhancement of ETS2 worsened ALI and activated the TGF-β1/Smad pathway. Moreover, elevation of ETS2 decreased miR-145-5p-mediated protection against ALI. Conclusion Evidently, miR-145-5p negatively regulates ETS2 expression and inactivates TGF-β1/Smad pathway to ameliorate ALI in rats.

Ventilator-Induced Lung Injury Is Associated with Neutrophil Infiltration, Macrophage Activation, and TGF-β1 mRNA Upregulation in Rat Lungs

2001 ◽  
Vol 92 (2) ◽  
pp. 428-436 ◽  
Author(s):  
Hideaki Imanaka ◽  
Motomu Shimaoka ◽  
Nariaki Matsuura ◽  
Masaji Nishimura ◽  
Noriyuki Ohta ◽  
...  
Keyword(s):  
Lung Injury ◽  
Macrophage Activation ◽  
Neutrophil Infiltration ◽  
Ventilator Induced Lung Injury ◽  
Rat Lungs ◽  
Tgf Β1

Losartan attenuates paraquat-induced pulmonary fibrosis in rats

2014 ◽  
Vol 34 (5) ◽  
pp. 497-505 ◽  
Author(s):  
F Guo ◽  
YB Sun ◽  
L Su ◽  
S Li ◽  
ZF Liu ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Injury ◽  
Mrna Expression ◽  
Collagen Type ◽  
Collagen Type I ◽  
Control Group ◽  
Type I ◽  
Expression Levels ◽  
Relative Expression ◽  
Tgf Β1

Paraquat (PQ) is one of the most widely used herbicides in the world and can cause pulmonary fibrosis in the cases with intoxication. Losartan, an angiotensin II type 1 receptor antagonist, has beneficial effects on the treatment of fibrosis. The aim of this study was to examine the effect of losartan on pulmonary fibrosis in PQ-intoxicated rats. Adult male Sprague Dawley rats ( n = 32, 180–220 g) were randomly assigned to four groups: (i) control group; (ii) PQ group; (iii) PQ + losartan 7d group; and (iv) PQ + losartan 14d group. Losartan treatment (intragastrically (i.g.), 10 mg/kg) was performed for 7 and 14 days after a single i.g. dose of 40 mg/kg PQ. All rats were killed on the 16th day, and hematoxylin–eosin and Masson’s trichrome staining were used to examine lung injury and fibrosis. The levels of hydroxyproline and transforming growth factor β1 (TGF-β1), matrix metallopeptidase 9 (Mmp9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) messenger RNA (mRNA) expression and relative expression levels of collagen type I and III were also detected. PQ caused a significant increase in hydroxyproline content, mRNA expression of TGF-β1, Mmp9, and TIMP-1, and relative expression levels of collagen type I and III (  p < 0.05), while losartan significantly decreased the amount of hydroxyproline and downregulated TGF-β1, Mmp9, and TIMP-1 mRNA and collagen type I and III expressions (  p < 0.05). Histological examination of PQ-treated rats showed lung injury and widespread inflammatory cell infiltration in the alveolar space and pulmonary fibrosis, while losartan could markedly reduce such damage and prevent pulmonary fibrosis. The results of this study indicated that losartan could reduce lung damage and prevent pulmonary fibrosis induced by PQ.

scholarly journals Protective Effects of Myrtol Standardized Against Radiation-Induced Lung Injury

2016 ◽  
Vol 38 (2) ◽  
pp. 619-634 ◽  
Author(s):  
De-yun Zhao ◽  
Hong-jin Qu ◽  
Jia-ming Guo ◽  
Hai-nan Zhao ◽  
Yan-yong Yang ◽  
...  
Keyword(s):  
Single Dose ◽  
Lung Injury ◽  
Major Complication ◽  
The Body ◽  
Protective Effects ◽  
Western Blot Assay ◽  
Tnf Α ◽  
Radiation Induced ◽  
The Impact ◽  
Tgf Β1

Background/Aims: As a major complication after thoracic radiotherapy, radiation-induced lung injury (RILI) has great impact on long term quality of life and could result in fatal respiratory insufficiency The present study was aimed to evaluate the effects of Myrtol standardized on RILI, and to investigate the underlying mechanism. Methods: A mouse model of radiation-induced lung injury was generated by using thoracic irradiation with a single dose of 16Gy. Mice were orally administrated with Myrtol (25 mg/kg/day) for 4 weeks after irradiation, while prednisone (5 mg/kg/day) was used as a positive control. After then, the body weight and lung coefficient were calculated. The severity of fibrosis was evaluated by observing pulmonary sections after radiation and collagen content in lung tissues was calculated following the hydroxyproline (HYP) assay. Pathological changes were observed in all the groups by using HE staining and Masson staining. The serum levels of TGF-β1, TNF-α, IL-1β, IL-6, and PGE2 were also measured with an ELISA assay. Western blot assay was used to measure the impact of Myrtol on AKT and its downstream signaling pathway, including MMP-2 and MMP-9. The levels of Vimentin and α-SMA were evaluated with an immunofluorescence assay. Results: Treatment with Myrtol standardized, but not prednisone, reduced lung coefficient and collagen deposition in lung tissues, while attenuated histological damages induced by irradiation. Myrtol standardized also reduced the production of MDA, while increased the level of SOD. It was also observed that Myrtol standardized inhibited TGF-β1 and a series of pro-inflammatory cytokines including TNF-α, IL-1β, IL-6, PGE2. While in prednisone group, even though the early pneumonitis was ameliorated, the collagen disposition remained unchanged in latter times. Immunofluorescence analysis also revealed elevation of vimentin and α-SMA in the alveoli after a single dose of 16Gy. Conclusion: The present results suggest Myrtol standardized as an effective agent for attenuating the lung injury induced by irradiation.

scholarly journals Atractylodin Suppresses TGF-β-Mediated Epithelial-Mesenchymal Transition in Alveolar Epithelial Cells and Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice

2021 ◽  
Vol 22 (20) ◽  
pp. 11152
Author(s):  
Kai-Wei Chang ◽  
Xiang Zhang ◽  
Shih-Chao Lin ◽  
Yu-Chao Lin ◽  
Chia-Hsiang Li ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Pulmonary Fibrosis ◽  
Lung Injury ◽  
Epithelial Mesenchymal Transition ◽  
A549 Cells ◽  
Alveolar Epithelial Cells ◽  
Collagen Deposition ◽  
Mesenchymal Transition ◽  
Alveolar Epithelial ◽  
Tgf Β1

Idiopathic pulmonary fibrosis (IPF) is characterized by fibrotic change in alveolar epithelial cells and leads to the irreversible deterioration of pulmonary function. Transforming growth factor-beta 1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in type 2 lung epithelial cells contributes to excessive collagen deposition and plays an important role in IPF. Atractylodin (ATL) is a kind of herbal medicine that has been proven to protect intestinal inflammation and attenuate acute lung injury. Our study aimed to determine whether EMT played a crucial role in the pathogenesis of pulmonary fibrosis and whether EMT can be utilized as a therapeutic target by ATL treatment to mitigate IPF. To address this topic, we took two steps to investigate: 1. Utilization of anin vitro EMT model by treating alveolar epithelial cells (A549 cells) with TGF-β1 followed by ATL treatment for elucidating the underlying pathways, including Smad2/3 hyperphosphorylation, mitogen-activated protein kinase (MAPK) pathway overexpression, Snail and Slug upregulation, and loss of E-cadherin. Utilization of an in vivo lung injury model by treating bleomycin on mice followed by ATL treatment to demonstrate the therapeutic effectiveness, such as, less collagen deposition and lower E-cadherin expression. In conclusion, ATL attenuates TGF-β1-induced EMT in A549 cells and bleomycin-induced pulmonary fibrosis in mice.

Anti-TGF-β1 antibody: An effective treatment for lung injury caused by paraquat in the future

2008 ◽  
Vol 70 (3) ◽  
pp. 705 ◽  
Author(s):  
Xiangdong Jian ◽  
Yanjun Ruan ◽  
Guangran Guo ◽  
Yuanchao Zhang
Keyword(s):  
Lung Injury ◽  
Effective Treatment ◽  
The Future ◽  
Tgf Β1

scholarly journals High tidal volume ventilation does not exacerbate acid-induced lung injury in infant rats

2013 ◽  
Vol 189 (1) ◽  
pp. 129-135 ◽  
Author(s):  
Peter D. Sly ◽  
Philip K. Nicholls ◽  
Luke J. Berry ◽  
Zoltán Hantos ◽  
Vincenzo Cannizzaro
Keyword(s):  
Lung Injury ◽  
Tidal Volume ◽  
High Tidal Volume ◽  
Infant Rats ◽  
High Tidal Volume Ventilation ◽  
Volume Ventilation

scholarly journals Effect of SIS3 on Extracellular Matrix Remodeling and Repair in a Lipopolysaccharide-Induced ARDS Rat Model

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Qiong Liang ◽  
Qiqing Lin ◽  
Yueyong Li ◽  
Weigui Luo ◽  
Xia Huang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Lung Injury ◽  
Rat Model ◽  
Intracellular Signaling ◽  
Disease Model ◽  
Intratracheal Instillation ◽  
Control Group ◽  
Matrix Remodeling ◽  
Phosphate Buffered Saline ◽  
Tgf Β1

The remodeling of the extracellular matrix (ECM) in the parenchyma plays an important role in the development of acute respiratory distress syndrome (ARDS), a disease characterized by lung injury. Although it is clear that TGF-β1 can modulate the expression of the extracellular matrix (ECM) through intracellular signaling molecules such as Smad3, its role as a therapeutic target against ARDS remains unknown. In this study, a rat model was established to mimic ARDS via intratracheal instillation of lipopolysaccharide (LPS). A selective inhibitor of Smad3 (SIS3) was intraperitoneally injected into the disease model, while phosphate-buffered saline (PBS) was used in the control group. Animal tissues were then evaluated using histological analysis, immunohistochemistry, RT-qPCR, ELISA, and western blotting. LPS was found to stimulate the expression of RAGE, TGF-β1, MMP2, and MMP9 in the rat model. Moreover, treatment with SIS3 was observed to reverse the expression of these molecules. In addition, pretreatment with SIS3 was shown to partially inhibit the phosphorylation of Smad3 and alleviate symptoms including lung injury and pulmonary edema. These findings indicate that SIS3, or the blocking of TGF-β/Smad3 pathways, could influence remodeling of the ECM and this may serve as a therapeutic strategy against ARDS.

scholarly journals Protective effects of ulinastatin and methylprednisolone against radiation-induced lung injury in mice

2016 ◽  
Vol 57 (5) ◽  
pp. 505-511 ◽  
Author(s):  
Yu Sun ◽  
Yu-Jun Du ◽  
Hui Zhao ◽  
Guo-Xing Zhang ◽  
Ni Sun ◽  
...  
Keyword(s):  
Lung Injury ◽  
Lung Tissue ◽  
Transforming Growth Factor ◽  
Lavage Fluid ◽  
Protective Effects ◽  
Pathological Changes ◽  
Tnf Α ◽  
Methylprednisolone Treatment ◽  
Radiation Induced ◽  
Tgf Β1

Abstract The effectiveness of ulinastatin and methylprednisolone in treating pathological changes in mice with radiation-induced lung injury (RILI) was evaluated. Forty C57BL/6 female mice received whole-chest radiation (1.5 Gy/min for 12 min) and were randomly allocated into Group R (single radiation, n =  10), Group U (ulinastatin treatment, n =  10), Group M (methylprednisolone treatment, n =  10), or Group UM (ulinastatin and methylprednisolone treatment, n =  10). Another 10 untreated mice served as controls (Group C). Pathological changes in lung tissue, pulmonary interstitial area density (PIAD) and expression levels of transforming growth factor β1 (TGF-β1) and tumor necrosis factor α (TNF-α) in lung tissue, serum and bronchoalveolar lavage fluid were determined. Alleviation of pathological changes in lung tissue was observed in Groups U, M and UM. Treatment with ulinastatin, methylprednisolone or both effectively delayed the development of fibrosis at 12 weeks after radiation. Ulinastatin, methylprednisolone or both could alleviate the radiation-induced increase in the PIAD ( P  &lt; 0.05 or P  &lt; 0.01). Treatment with ulinastatin, methylprednisolone or both significantly reduced the expression of TNF-α, but not TGF-β1, at 9 weeks after radiation compared with Group R ( P  &lt; 0.01). Ulinastatin and / or methylprednisolone effectively decreased the level of TNF-α in lung tissue after RILI and inhibited both the inflammatory response and the development of fibrosis.

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