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 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

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

Eosinophil Cationic Protein Stimulates TGF-β1 Release by Human Lung Fibroblasts In Vitro

Inflammation ◽  
2007 ◽  
Vol 30 (5) ◽  
pp. 153-160 ◽  
Author(s):  
Ulrika Zagai ◽  
Elham Dadfar ◽  
Joachim Lundahl ◽  
Per Venge ◽  
C. Magnus Sköld
Keyword(s):  
Human Lung ◽  
Eosinophil Cationic Protein ◽  
Lung Fibroblasts ◽  
Cationic Protein ◽  
Human Lung Fibroblasts ◽  
Tgf Β1

scholarly journals Fibroblast to Myofibroblast Transition is Enhanced by Increased Cell Density

2021 ◽  
Author(s):  
Mary T. Doolin ◽  
Ian M. Smith ◽  
Kimberly M. Stroka
Keyword(s):  
Extracellular Matrix ◽  
Cell Density ◽  
Human Lung ◽  
Collagen Matrix ◽  
Lung Fibroblasts ◽  
Low Density ◽  
Human Lung Fibroblasts ◽  
Activated Fibroblasts ◽  
Tgf Β1

Idiopathic pulmonary fibrosis (IPF) is a chronic disease of the lung caused by a rampant inflammatory response that results in the deposition of excessive extracellular matrix (ECM). IPF patient lungs also develop fibroblastic foci that consist of activated fibroblasts and myofibroblasts. In concert with ECM deposition, the increased cell density within fibroblastic foci imposes confining forces on lung fibroblasts. In this work, we observed that increased cell density increases the incidence of fibroblast to myofibroblast transition (FMT), but mechanical confinement imposed by micropillars has no effect on FMT incidence. We found that human lung fibroblasts (HLFs) express more α-SMA and deposit more collagen matrix, which are both characteristics of myofibroblasts, in response to TGF-β1 when cells were seeded at a high density compared to a medium or a low density. These results support the hypothesis that HLFs undergo FMT more readily in response to TGF-β1 when cells are densely packed, and this effect could be dependent on increased OB-cadherin expression. This work demonstrates that cell density is an important factor to consider when modelling IPF in vitro, and it may suggest decreasing cell density within fibroblastic foci as a strategy to reduce IPF burden.

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