scholarly journals Methylation-mediated BMPER expression in fibroblast activation in vitro and lung fibrosis in mice in vivo

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Caijuan Huan ◽  
Ting Yang ◽  
Jiurong Liang ◽  
Ting Xie ◽  
Luis Cheng ◽  
...  
Keyword(s):  
Lung Fibrosis ◽  
Fibroblast Activation

scholarly journals Bortezomib inhibits lung fibrosis and fibroblast activation without proteasome inhibition

2021 ◽  
Author(s):  
Loka Raghu Kumar Penke ◽  
Jennifer Speth ◽  
Scott Wettlaufer ◽  
Christina Draijer ◽  
Marc Peters-Golden
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Fibrosis ◽  
Proteasome Inhibition ◽  
Fibroblast Activation ◽  
Dual Specificity ◽  
Therapeutic Administration ◽  
Proteasomal Inhibitor ◽  
Characteristic Resistance

The FDA-approved proteasomal inhibitor bortezomib (BTZ) has attracted interest for its potential anti-fibrotic actions. However, neither its in vivo efficacy in lung fibrosis nor its dependence on proteasome inhibition has been conclusively defined. Herein, we identify that therapeutic administration of BTZ in a mouse model of pulmonary fibrosis diminished the severity of fibrosis without reducing proteasome activity in the lung. Under conditions designed to mimic this lack of proteasome inhibition in vitro, it reduced fibroblast proliferation, differentiation into myofibroblasts, and collagen synthesis. It promoted de-differentiation of myofibroblasts and overcame their characteristic resistance to apoptosis. Mechanistically, BTZ inhibited kinases important for fibroblast activation while inducing expression of dual-specificity phosphatase 1 or DUSP1, and knockdown of DUSP1 abolished its anti-fibrotic actions in fibroblasts. Our findings identify a novel proteasome-independent mechanism of anti-fibrotic actions for BTZ and support its therapeutic repurposing for pulmonary fibrosis.

scholarly journals Fibroblast activation protein targeted near infrared photoimmunotherapy (NIR PIT) overcomes therapeutic resistance in human esophageal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryoichi Katsube ◽  
Kazuhiro Noma ◽  
Toshiaki Ohara ◽  
Noriyuki Nishiwaki ◽  
Teruki Kobayashi ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Near Infrared ◽  
Fibroblast Activation Protein ◽  
Therapeutic Resistance ◽  
Fibroblast Activation ◽  
Human Esophageal Cancer

AbstractCancer-associated fibroblasts (CAFs) have an important role in the tumor microenvironment. CAFs have the multifunctionality which strongly support cancer progression and the acquisition of therapeutic resistance by cancer cells. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that uses a highly selective monoclonal antibody (mAb)-photosensitizer conjugate. We developed fibroblast activation protein (FAP)-targeted NIR-PIT, in which IR700 was conjugated to a FAP-specific antibody to target CAFs (CAFs-targeted NIR-PIT: CAFs-PIT). Thus, we hypothesized that the control of CAFs could overcome the resistance to conventional chemotherapy in esophageal cancer (EC). In this study, we evaluated whether EC cell acquisition of stronger malignant characteristics and refractoriness to chemoradiotherapy are mediated by CAFs. Next, we assessed whether the resistance could be rescued by eliminating CAF stimulation by CAFs-PIT in vitro and in vivo. Cancer cells acquired chemoradiotherapy resistance via CAF stimulation in vitro and 5-fluorouracil (FU) resistance in CAF-coinoculated tumor models in vivo. CAF stimulation promoted the migration/invasion of cancer cells and a stem-like phenotype in vitro, which were rescued by elimination of CAF stimulation. CAFs-PIT had a highly selective effect on CAFs in vitro. Finally, CAF elimination by CAFs-PIT in vivo demonstrated that the combination of 5-FU and NIR-PIT succeeded in producing 70.9% tumor reduction, while 5-FU alone achieved only 13.3% reduction, suggesting the recovery of 5-FU sensitivity in CAF-rich tumors. In conclusion, CAFs-PIT could overcome therapeutic resistance via CAF elimination. The combined use of novel targeted CAFs-PIT with conventional anticancer treatments can be expected to provide a more effective and sensible treatment strategy.

Fucoxanthin inhibits profibrotic protein expression in vitro and attenuates bleomycin-induced lung fibrosis in vivo

2017 ◽  
Vol 811 ◽  
pp. 199-207 ◽  
Author(s):  
Sun Young Ma ◽  
Won Sun Park ◽  
Dae-Sung Lee ◽  
Grace Choi ◽  
Mi-Jin Yim ◽  
...  
Keyword(s):  
Protein Expression ◽  
Lung Fibrosis

scholarly journals Residual sodium dodecyl sulfate in decellularized muscle matrices leads to fibroblast activation in vitro and foreign body response in vivo

2017 ◽  
Vol 12 (3) ◽  
Author(s):  
Emily E. Friedrich ◽  
Steven T. Lanier ◽  
Solmaz Niknam‐Bienia ◽  
Gabriel A. Arenas ◽  
Divya Rajendran ◽  
...  
Keyword(s):  
Foreign Body ◽  
Sodium Dodecyl Sulfate ◽  
Sodium Dodecyl ◽  
Foreign Body Response ◽  
Fibroblast Activation ◽  
Dodecyl Sulfate ◽  
Body Response

Antifibrotic properties of caveolin-1 scaffolding domain in vitro and in vivo

2008 ◽  
Vol 294 (5) ◽  
pp. L843-L861 ◽  
Author(s):  
Elena Tourkina ◽  
Mathieu Richard ◽  
Pal Gööz ◽  
Michael Bonner ◽  
Jaspreet Pannu ◽  
...  
Keyword(s):  
Lung Fibrosis ◽  
Smooth Muscle Actin ◽  
Lung Fibroblasts ◽  
Normal Lung ◽  
Signaling Molecule ◽  
Caveolin 1 ◽  
Tenascin C ◽  
Ecm Proteins

Lung fibrosis involves the overexpression of ECM proteins, primarily collagen, by α-smooth muscle actin (ASMA)-positive cells. Caveolin-1 is a master regulator of collagen expression by cultured lung fibroblasts and of lung fibrosis in vivo. A peptide equivalent to the caveolin-1 scaffolding domain (CSD peptide) inhibits collagen and tenascin-C expression by normal lung fibroblasts (NLF) and fibroblasts from the fibrotic lungs of scleroderma patients (SLF). CSD peptide inhibits ASMA expression in SLF but not NLF. Similar inhibition of collagen, tenascin-C, and ASMA expression was also observed when caveolin-1 expression was upregulated using adenovirus. These observations suggest that the low caveolin-1 levels in SLF cause their overexpression of collagen, tenascin-C, and ASMA. In mechanistic studies, MEK, ERK, JNK, and Akt were hyperactivated in SLF, and CSD peptide inhibited their activation and altered their subcellular localization. These studies and experiments using kinase inhibitors suggest many differences between NLF and SLF in signaling cascades. To validate these data, we determined that the alterations in signaling molecule activation observed in SLF also occur in fibrotic lung tissue from scleroderma patients and in mice with bleomycin-induced lung fibrosis. Finally, we demonstrated that systemic administration of CSD peptide to bleomycin-treated mice blocks epithelial cell apoptosis, inflammatory cell infiltration, and changes in tissue morphology as well as signaling molecule activation and collagen, tenascin-C, and ASMA expression associated with lung fibrosis. CSD peptide may be a prototype for novel treatments for human lung fibrosis that act, in part, by inhibiting the expression of ASMA and ECM proteins.

Maresin 1 Inhibits Epithelial-to-Mesenchymal Transition in Vitro and Attenuates Bleomycin Induced Lung Fibrosis in Vivo

Shock ◽  
2015 ◽  
Vol 44 (5) ◽  
pp. 496-502 ◽  
Author(s):  
Yaxin Wang ◽  
Ruidong Li ◽  
Lin Chen ◽  
Wen Tan ◽  
Zhipeng Sun ◽  
...  
Keyword(s):  
Lung Fibrosis ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Maresin 1

scholarly journals The Role of PPAR Gamma in Systemic Sclerosis

PPAR Research ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Andréa Tavares Dantas ◽  
Michelly Cristiny Pereira ◽  
Moacyr Jesus Barreto de Melo Rego ◽  
Laurindo Ferreira da Rocha ◽  
Ivan da Rocha Pitta ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Lung Fibrosis ◽  
Ppar Gamma ◽  
Immune Dysregulation ◽  
Unknown Etiology ◽  
Internal Organs ◽  
Medical Need

Fibrosis is recognized as an important feature of many chronic diseases, such as systemic sclerosis (SSc), an autoimmune disease of unknown etiology, characterized by immune dysregulation and vascular injury, followed by progressive fibrosis affecting the skin and multiple internal organs. SSc has a poor prognosis because no therapy has been shown to reverse or arrest the progression of fibrosis, representing a major unmet medical need. Recently, antifibrotic effects of PPARγligands have been studiedin vitroandin vivoand some theories have emerged leading to new insights. Aberrant PPARγfunction seems to be implicated in pathological fibrosis in the skin and lungs. This antifibrotic effect is mainly related to the inhibition of TGF-β/Smad signal transduction but other pathways can be involved. This review focused on recent studies that identified PPARγas an important novel pathway with critical roles in regulating connective tissue homeostasis, with emphasis on skin and lung fibrosis and its role on systemic sclerosis.

scholarly journals Arctigenin Suppressed Epithelial-Mesenchymal Transition Through Wnt3a/β-Catenin Pathway in PQ-Induced Pulmonary Fibrosis

2020 ◽  
Vol 11 ◽  
Author(s):  
Fei Gao ◽  
Yun Zhang ◽  
Zhizhou Yang ◽  
Mengmeng Wang ◽  
Zhiyi Zhou ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Lung Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
A549 Cells ◽  
Underlying Mechanism ◽  
Alveolar Type ◽  
Mesenchymal Transition

Arctigenin (ATG), a major bioactive substance of Fructus Arctii, counters renal fibrosis; however, whether it protects against paraquat (PQ)-induced lung fibrosis remains unknown. The present study was to determine the effect of ATG on PQ-induced lung fibrosis in a mouse model and the underlying mechanism. Firstly, we found that ATG suppressed PQ-induced pulmonary fibrosis by blocking the epithelial-mesenchymal transition (EMT). ATG reduced the expressions of Vimentin and α-SMA (lung fibrosis markers) induced by PQ and restored the expressions of E-cadherin and Occludin (two epithelial markers) in vivo and in vitro. Besides, the Wnt3a/β-catenin signaling pathway was significantly activated in PQ induced pulmonary fibrosis. Further analysis showed that pretreatment of ATG profoundly abrogated PQ-induced EMT-like phenotypes and behaviors in A549 cells. The Wnt3a/β-catenin signaling pathway was repressed by ATG treatment. The overexpression of Wnt3a could weaken the therapeutic effect of ATG in A549 cells. These findings suggested that ATG could serve as a new therapeutic candidate to inhibit or even reverse EMT-like changes in alveolar type II cells during PQ-induced lung fibrosis, and unraveled that the Wnt3a/β-catenin pathway might be a mechanistic tool for ATG to control pulmonary fibrosis.

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