scholarly journals LncRNA-RP11 Modulates TGF-β1-Activated Radiation-Induced Lung Injury Through Downregulating microRNA-29a

Dose-Response ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 155932582094907
Author(s):  
Xi Yang ◽  
Jianjiao Ni ◽  
Yida Li ◽  
Liqing Zou ◽  
Tiantian Guo ◽  
...  
Keyword(s):  
Lung Injury ◽  
Human Lung ◽  
Human Fibroblasts ◽  
Bioinformatic Analysis ◽  
Fine Tuning ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts ◽  
Thoracic Radiation ◽  
Radiation Induced ◽  
Tgf Β1

Radiation-induced lung injury (RILI) is one of the most serious complications of thoracic radiation and TGF-β1 is a central regulator of RILI. However, the molecular mechanism underlying the fine tuning of TGF-β1 signaling in RILI has not been fully understood. In the current study, differentially expressed long non-coding RNAs (LncRNAs) among human lung fibroblasts cell lines HFL-1 and WI-38 treated with TGF-β1, were identified by microarray and validated by real time PCR. LncRNA-RP11 was found to be the most increased LncRNA and it mediated the promotion of fibrogenic activity in human lung fibroblasts after TGF-β1 treatment. Bioinformatic analysis revealed that TGF-β1 may be associated with the component and structure of extracellular matrix in lung fibroblasts cells, and LncRNA-RP11 was predicted and confirmed to be a competing endogenous RNA by directly binding to miR-29a. Functional experiments investigating the biological role of LncRNA-RP11/miR-29a axis in RILI, were then carried out in human fibroblasts. The results showed that radiation promoted the expression of LncRNA-RP11, but regressed the expression of miR-29a. Furthermore, radiation elevated the expression of various common collagenic proteins, which could be abolished by overexpression of miR-29a.

scholarly journals Identification of TGF-β receptor-1 as a key regulator of carbon nanotube-induced fibrogenesis

2015 ◽  
Vol 309 (8) ◽  
pp. L821-L833 ◽  
Author(s):  
Anurag Mishra ◽  
Todd A. Stueckle ◽  
Robert R. Mercer ◽  
Raymond Derk ◽  
Yon Rojanasakul ◽  
...  
Keyword(s):  
Lung Fibrosis ◽  
Human Lung ◽  
Lung Fibroblasts ◽  
Screening Tests ◽  
Rapid Screening ◽  
Interstitial Tissue ◽  
Collagen Production ◽  
Human Lung Fibroblasts ◽  
Β Receptor ◽  
Tgf Β1

Carbon nanotubes (CNTs) induce rapid interstitial lung fibrosis, but the underlying mechanisms are unclear. Previous studies indicated that the ability of CNTs to penetrate lung epithelium, enter interstitial tissue, and stimulate fibroblasts to produce collagen matrix is important to lung fibrosis. In this study, we investigated the activation of transforming growth factor-β receptor-1 [TGF-β R1; i.e., activin receptor-like kinase 5 (ALK5) receptor] and TGF-β/Smad signaling pathway in CNT-induced collagen production in human lung fibroblasts. Human lung fibroblasts and epithelial cells were exposed to low, physiologically relevant concentrations (0.02–0.6 μg/cm2) of single-walled CNTs (SWCNT) and multiwalled CNTs (MWCNT) in culture and analyzed for collagen, TGF-β1, TGF-β R1, and SMAD proteins by Western blotting and immunofluorescence. Chemical inhibition of ALK5 and short-hairpin (sh) RNA targeting of TGF-β R1 and Smad2 were used to probe the fibrogenic mechanism of CNTs. Both SWCNT and MWCNT induced an overexpression of TGF-β1, TGF-β R1 and Smad2/3 proteins in lung fibroblasts compared with vehicle or ultrafine carbon black-exposed controls. SWCNT- and MWCNT-induced collagen production was blocked by ALK5 inhibitor or shRNA knockdown of TGF-β R1 and Smad2. Our results indicate the critical role of TGF-β R1/Smad2/3 signaling in CNT-induced fibrogenesis by upregulating collagen production in lung fibroblasts. This novel finding may aid in the design of mechanism-based risk assessment and development of rapid screening tests for nanomaterial fibrogenicity.

TGF-β1 Induces Tissue Factor Expression in Human Lung Fibroblasts in a PI3K/JNK/Akt-Dependent and AP-1–Dependent Manner

2012 ◽  
Vol 47 (5) ◽  
pp. 614-627 ◽  
Author(s):  
Malgorzata Wygrecka ◽  
Dariusz Zakrzewicz ◽  
Brigitte Taborski ◽  
Miroslava Didiasova ◽  
Grazyna Kwapiszewska ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Human Lung ◽  
Lung Fibroblasts ◽  
Dependent Manner ◽  
Tissue Factor Expression ◽  
Human Lung Fibroblasts ◽  
Factor Expression ◽  
Tgf Β1

TGF-β1 targets the GSK-3β/β-catenin pathway via ERK activation in the transition of human lung fibroblasts into myofibroblasts

2008 ◽  
Vol 57 (4) ◽  
pp. 274-282 ◽  
Author(s):  
F CARACI ◽  
E GILI ◽  
M CALAFIORE ◽  
M FAILLA ◽  
C LAROSA ◽  
...  
Keyword(s):  
Human Lung ◽  
Lung Fibroblasts ◽  
Erk Activation ◽  
Human Lung Fibroblasts ◽  
Gsk 3Β ◽  
Tgf Β1

scholarly journals Platelet-activating factor exerts mitogenic activity and stimulates expression of interleukin 6 and interleukin 8 in human lung fibroblasts via binding to its functional receptor.

1996 ◽  
Vol 184 (1) ◽  
pp. 191-201 ◽  
Author(s):  
M Roth ◽  
M Nauck ◽  
S Yousefi ◽  
M Tamm ◽  
K Blaser ◽  
...  
Keyword(s):  
Pertussis Toxin ◽  
Tyrosine Kinases ◽  
Human Lung ◽  
Human Fibroblasts ◽  
Platelet Activating Factor ◽  
Lung Fibroblasts ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Human Lung Fibroblasts ◽  
Paf Receptor

Platelet-activating factor (PAF) is a potent proinflammatory phospholipid mediator of the lung. In this study, we demonstrate that PAF receptor mRNA and protein is expressed by human lung fibroblasts. Interaction of PAF with its specific receptor resulted in increases of tyrosine phosphorylation of several intracellular proteins, indicating that the PAF-receptor might be functionally active. PAF-induced transcription of protooncogenes c-fos and c-jun as well as of interleukin (IL)-6 and IL-8 genes in human fibroblasts. Transcription of the interleukins was followed by secretion of the respective proteins. Moreover, PAF enhanced proliferation of fibroblasts in a concentration-dependent manner. Using signaling inhibitors, we demonstrate that PAF-induced transcription of the c-fos, IL-6, and IL-8 genes, as well as proliferation, require activation of pertussis toxin-sensitive G proteins, tyrosine kinases, and protein kinase C (PKC). In contrast, transcription of c-jun was blocked by pertussis toxin, but not by inhibitors for tyrosine kinases or PKC. These data suggest that PAF stimulates distinct signaling pathways in human lung fibroblasts. In addition, the activation of human fibroblasts by PAF leads to enhanced proliferation and to the expression of proinflammatory cytokines, which may contribute to the pathophysiological changes in pulmonary inflammation.

scholarly journals Ninjinyoeito Ameliorated Cigarette Smoke Extract-induced Apoptosis and Inflammation Through JNK Signaling Inhibition in Human Lung Fibroblasts

2021 ◽  
Author(s):  
Kenta Murata ◽  
Nina Fujita ◽  
Ryuji Takahashi
Keyword(s):  
Lung Injury ◽  
Cigarette Smoke ◽  
Human Lung ◽  
Cigarette Smoke Extract ◽  
Lung Fibroblasts ◽  
Ros Production ◽  
Jnk Signaling ◽  
Human Lung Fibroblasts ◽  
Induced Apoptosis ◽  
Apoptosis And Inflammation

Abstract BackgroundCigarette smoke is a major risk factor for various lung diseases, such as chronic obstructive pulmonary disease (COPD). Ninjinyoeito (NYT), a traditional Chinese medicine, has been prescribed for patients with post-illness or post-operative weakness, fatigue, loss of appetite, rash, cold limbs, and anemia. In addition to its traditional use, NYT has been prescribed for treating frailty in gastrointestinal, respiratory, and urinary functions. Further, NYT treatment can ameliorate cigarette smoke-induced lung injury, which is a destructive index in mice; however, the detailed underlying mechanism remains unknown. PurposeThe purpose of this study was to investigate whether NYT ameliorates cigarette smoke-induced lung injury and inflammation in human lung fibroblasts and determine its mechanism of action. MethodsWe prepared a cigarette smoke extract (CSE) from commercially available cigarettes to induce cell injury and inflammation in the human lung fibroblast cell line HFL1. The cells were pretreated with NYT for 24 h prior to CSE exposure. Cytotoxicity and cell viability were measured by lactate dehydrogenase (LDH) cytotoxicity assay and cell counting kit (CCK)-8. IL-8 level in the cell culture medium was measured by performing Enzyme-Linked Immuno Sorbent Assay (ELISA). To clarify the mechanisms of NYT, we used CellROX Green Reagent for reactive oxygen species (ROS) production and western blotting analysis for cell signaling.ResultsExposure of HFL1 cells to CSE for 24 h induced apoptosis and interleukin (IL)-8 release. Pretreatment with NYT inhibited apoptosis and IL-8 release. Furthermore, CSE exposure for 24 h increased the production of ROS and phosphorylation levels of p38 and JNK. Pretreatment with NYT only inhibited CSE-induced JNK phosphorylation, and not ROS production and p38 phosphorylation. These results suggest that NYT acts as a JNK-specific inhibitor.ConclusionNYT treatment ameliorated CSE-induced apoptosis and inflammation by inhibiting the JNK signaling pathway. Finally, these results suggest that NYT may be a promising therapeutic agent for patients with COPD.

scholarly journals 5-Aminosalicylic acid Attenuates Paraquat-induced Lung Fibroblasts Activation and Pulmonary Fibrosis of Rats

2021 ◽  
Author(s):  
Hui Chen ◽  
Jinfeng Cui ◽  
Juan Wang ◽  
Yuan Wang ◽  
Fei Tong ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Human Lung ◽  
Lung Fibroblasts ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Aminosalicylic Acid ◽  
Human Lung Fibroblasts ◽  
Group 5 ◽  
Tgf Β1

Abstract Pulmonary fibrosis is one of the most common complications of paraquat (PQ) poisoning, which becomes the focus of treatment. More and more studies have found that 5-Aminosalicylic acid (5-ASA) may be a prospective therapy against fibrotic diseases. In the present study, we observed whether 5-ASA could attenuate the pulmonary fibrosis in PQ-treated rats and human lung fibroblasts (WI38VA13) cells, and subsequently explored the possible underlying mechanisms. Wistar rats were divided into control group, 5-ASA group, PQ group and PQ + 5-ASA group. Rats were sacrificed on 3, 7, 14, and 28 days after PQ treatment. We observed pulmonary histopathological changes and fibrosis formation among different groups through hematoxylin and eosin (H&E) and Masson staining and TGF-β1, p-Smad3 and the peroxisome proliferator activated receptor γ (PPARγ) pulmonary content via immunohistochemical staining and Western blot. In addition, human lung fibroblasts WI38VA13 were also divided into control group, PQ group, 5-ASA group and PQ + 5-ASA group. And the role of TGF-β1 signaling pathway regulated factors (TGF-β1, p-Smad3 and PPARγ) were explored. Treatment with 5-ASA significantly inhibited the PQ-induced activation of TGF-β1 signaling pathway in human lung fibroblasts WI38VA13 cells. In conclusion, the results of this study suggested that 5-ASA has potential value in the treatment of PQ-induced pulmonary fibrosis via suppressing the activation of TGF-β1 signaling pathway.

Smad3 mediates TGF-β1-induced collagen gel contraction by human lung fibroblasts

2006 ◽  
Vol 339 (1) ◽  
pp. 290-295 ◽  
Author(s):  
Tetsu Kobayashi ◽  
Xiangde Liu ◽  
Fu-Qiang Wen ◽  
Tadashi Kohyama ◽  
Lei Shen ◽  
...  
Keyword(s):  
Human Lung ◽  
Collagen Gel ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts ◽  
Collagen Gel Contraction ◽  
Tgf Β1

Pirfenidone inhibits the expression of HSP47 in TGF-β1-stimulated human lung fibroblasts

Life Sciences ◽  
2008 ◽  
Vol 82 (3-4) ◽  
pp. 210-217 ◽  
Author(s):  
Seiko Nakayama ◽  
Hiroshi Mukae ◽  
Noriho Sakamoto ◽  
Tomoyuki Kakugawa ◽  
Sumako Yoshioka ◽  
...  
Keyword(s):  
Human Lung ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts ◽  
Tgf Β1

scholarly journals Membrane-associated chondroitin sulfate proteoglycans of human lung fibroblasts.

1989 ◽  
Vol 108 (3) ◽  
pp. 1165-1173 ◽  
Author(s):  
G David ◽  
V Lories ◽  
A Heremans ◽  
B Van der Schueren ◽  
J J Cassiman ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Human Lung ◽  
Core Protein ◽  
Human Fibroblasts ◽  
Chondroitin Sulfate Proteoglycans ◽  
Lung Fibroblasts ◽  
Hydrophobic Membrane ◽  
Human Lung Fibroblasts ◽  
Core Proteins

Cultured human fetal lung fibroblasts produce some chondroitin sulfate proteoglycans that are extracted as an aggregate in chaotropic buffers containing 4 M guanidinium chloride. The aggregated proteoglycans are excluded from Sepharose CL4B and 2B, but become included, eluting with a Kav value of 0.53 from Sepharose CL4B, when Triton X-100 is included in the buffer. Conversely, some of the detergent-extractable chondroitin sulfate proteoglycans can be incorporated into liposomes, suggesting the existence of a hydrophobic membrane-intercalated chondroitin sulfate proteoglycan fraction. Purified preparations of hydrophobic chondroitin sulfate proteoglycans contain two major core protein forms of 90 and 52 kD. A monoclonal antibody (F58-7D8) obtained from the fusion of myeloma cells with spleen cells of BALB/c mice that were immunized with hydrophobic proteoglycans recognized the 90- but not the 52-kD core protein. The epitope that is recognized by the antibody is exposed at the surface of cultured human lung fibroblasts and at the surface of several stromal cells in vivo, but also at the surface of Kupffer cells and of epidermal cells. The core proteins of these small membrane-associated chondroitin sulfate proteoglycans are probably distinct from those previously identified in human fibroblasts by biochemical, immunological, and molecular biological approaches.

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