Metalloproteinase and growth factor interactions: do they play a role in pulmonary fibrosis?

2002 ◽  
Vol 283 (1) ◽  
pp. L1-L11 ◽  
Author(s):  
Margaret K. Winkler ◽  
John L. Fowlkes
Keyword(s):  
Acute Lung Injury ◽  
Growth Factors ◽  
Growth Factor ◽  
Pulmonary Fibrosis ◽  
Lung Injury ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Inflammatory Cells ◽  
Transforming Growth Factor Β ◽  
Target Cells

Chronic lung disease due to interstitial fibrosis can be a consequence of acute lung injury and inflammation. The inflammatory response is mediated through the migration of inflammatory cells, actions of proinflammatory cytokines, and the secretion of matrix-degrading proteinases. After the initial inflammatory insult, successful healing of the lung may occur, or alternatively, dysregulated tissue repair can result in scarring and fibrosis. On the basis of recent insights into the mechanisms underlying acute lung injury and its long-term consequences, data suggest that proteinases, such as the matrix metalloproteinases (MMPs), may not only be involved in the breakdown and remodeling that occurs during the injury but may also cause the release of growth factors and cytokines known to influence growth and differentiation of target cells within the lung. Through the release of and activation of fibrosis-promoting cytokines and growth factors such as transforming growth factor-β1, tumor necrosis factor-α, and insulin-like growth factors by MMPs, we propose that these metalloproteinases may be integral to the initiation and progression of pulmonary fibrosis.

Role of growth factors in acute lung injury induced by paraquat in a rat model

2010 ◽  
Vol 30 (6) ◽  
pp. 460-469 ◽  
Author(s):  
Xiangdong Jian ◽  
Ming Li ◽  
Yijing Zhang ◽  
Yanjun Ruan ◽  
Guangran Guo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lung Injury ◽  
Growth Factors ◽  
Growth Factor ◽  
Lung Injury ◽  
Rat Model ◽  
Transforming Growth Factor ◽  
Pcr Analysis ◽  
Circulatory Level

Paraquat (PQ) can cause acute lung injury in humans and experimental animals. However, the role of growth factors in the progression of injury has not been clearly established. We developed an animal model of PQ-induced lung injury using Wistar rats. One milliliter of PQ solution (30, 60, and 120 mg/kg) was applied through the lavage, while the same amount of vehicle was applied to control rats. Based on histopathology, the lungs of some animals exposed to PQ showed acute fulmination, resulting in death, while others showed a more protracted injury, resulting in typical pulmonary fibrosis at 21 days. Using this PQ-poisoned rat model, we examined the intrapulmonary gene expression and circulatory level of cytokines and growth factors at 8 hours, 24 hours, 3 days, 7 days, 14 days, and 21 days after PQ administration. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that the gene expression levels of interleukin-1 beta and interleukin-6 were significantly increased at 21 days after PQ challenge compared with the controls. The mRNA expression of tumor necrosis factor-alpha was also significantly increased except on days 14 and 21 after PQ treatment. Moreover, PQ-treated rats showed enhanced gene expression of growth factors such as platelet-derived growth factor-A and insulin-like growth factor-1 at 21 days and transforming growth factor-beta 1 at 14 days. ELISA results showed the circulatory level of cytokines and growth factors coincided with intrapulmonary gene expression. The synergistic effects of these molecules are presumed to cause pulmonary damage due to PQ challenge and may become targets of treatment.

scholarly journals Gene Expression Changes during the Development of Acute Lung Injury Role of Transforming Growth Factor β

2005 ◽  
Vol 172 (11) ◽  
pp. 1399-1411 ◽  
Author(s):  
Scott C. Wesselkamper ◽  
Lisa M. Case ◽  
Lisa N. Henning ◽  
Michael T. Borchers ◽  
Jay W. Tichelaar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lung Injury ◽  
Growth Factor ◽  
Lung Injury ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β

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.

scholarly journals Changes in cardiac resident fibroblast physiology and phenotype in aging

2018 ◽  
Vol 315 (4) ◽  
pp. H745-H755 ◽  
Author(s):  
JoAnn Trial ◽  
Katarzyna A. Cieslik
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Cardiac Fibroblasts ◽  
Transforming Growth Factor Β ◽  
Tissue Homeostasis ◽  
Apparent Paradox ◽  
Smad Pathway ◽  
Activated Fibroblasts ◽  
Resident Fibroblast

The cardiac fibroblast plays a central role in tissue homeostasis and in repair after injury. With aging, dysregulated cardiac fibroblasts have a reduced capacity to activate a canonical transforming growth factor-β-Smad pathway and differentiate poorly into contractile myofibroblasts. That results in the formation of an insufficient scar after myocardial infarction. In contrast, in the uninjured aged heart, fibroblasts are activated and acquire a profibrotic phenotype that leads to interstitial fibrosis, ventricular stiffness, and diastolic dysfunction, all conditions that may lead to heart failure. There is an apparent paradox in aging, wherein reparative fibrosis is impaired but interstitial, adverse fibrosis is augmented. This could be explained by analyzing the effectiveness of signaling pathways in resident fibroblasts from young versus aged hearts. Whereas defective signaling by transforming growth factor-β leads to insufficient scar formation by myofibroblasts, enhanced activation of the ERK1/2 pathway may be responsible for interstitial fibrosis mediated by activated fibroblasts. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/fibroblast-phenotypic-changes-in-the-aging-heart/ .

scholarly journals Knockdown of Long Noncoding RNA H19 Represses the Progress of Pulmonary Fibrosis through the Transforming Growth Factor β/Smad3 Pathway by Regulating MicroRNA 140

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
Xi Wang ◽  
Zhe Cheng ◽  
Lingling Dai ◽  
Tianci Jiang ◽  
Liuqun Jia ◽  
...  
Keyword(s):  
Growth Factor ◽  
Pulmonary Fibrosis ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Animal Experiments ◽  
A549 Cells ◽  
Transforming Growth Factor Β ◽  
Tgf Β1

ABSTRACT Long noncoding RNAs (lncRNAs) are involved in various human diseases. Recently, H19 was reported to be upregulated in fibrotic rat lung and play a stimulative role in bleomycin (BLM)-induced pulmonary fibrosis in mice. However, its expression in human fibrotic lung tissues and mechanism of action remain unclear. Here, our observations showed that H19 expression was significantly upregulated and that of microRNA 140 (miR-140) was markedly reduced in pulmonary fibrotic tissues from idiopathic pulmonary fibrosis (IPF) patients and transforming growth factor β1 (TGF-β1)-induced HBE and A549 cells. Moreover, the expression of H19 was negatively correlated with the expression of miR-140 in IPF tissues. H19 knockdown attenuated TGF-β1-induced pulmonary fibrosis in vitro. Furthermore, animal experiments showed that H19 knockdown attenuated BLM-induced pulmonary fibrosis in mice. The study of molecular mechanisms showed that H19 functioned via reduction of miR-140 expression by binding to miR-140. The increase of miR-140 inhibited TGF-β1-induced pulmonary fibrosis, and H19 upregulation diminished the inhibitory effects of miR-140 on TGF-β1-induced pulmonary fibrosis, which was involved in the TGF-β/Smad3 pathway. Taken together, our findings showed that H19 knockdown attenuated pulmonary fibrosis via the regulatory network of lncRNA H19–miR-140–TGF-β/Smad3 signaling, and H19 and miR-140 might represent therapeutic targets and early diagnostic and prognostic biomarkers for patients with pulmonary fibrosis.

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