scholarly journals NRF2 Activation Inhibits Both TGF-β1- and IL-13-Mediated Periostin Expression in Fibroblasts: Benefit of Cinnamaldehyde for Antifibrotic Treatment

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yasutaka Mitamura ◽  
Mika Murai ◽  
Chikage Mitoma ◽  
Masutaka Furue
Keyword(s):  
Dermal Fibroblasts ◽  
Treatment Modalities ◽  
Oxygen Species ◽  
Extracellular Matrix Component ◽  
Fibrotic Disease ◽  
Matrix Component ◽  
Nrf2 Activation ◽  
Life Threatening ◽  
Fibrotic Diseases ◽  
Tgf Β1

Systemic fibrosing or sclerotic disorders are life-threatening, but only very limited treatment modalities are available for them. In recent years, periostin (POSTN), a major extracellular matrix component, was established by several studies as a novel key player in the progression of systemic fibrotic disease. In this research, we revealed the involvement of oxidative stress in the expression of POSTN induced by TGF-β1 and IL-13 in dermal fibroblasts. We found that the antioxidant cinnamaldehyde activated the NRF2/HMOX1 pathway. Cinnamaldehyde also alleviated TGF-β1- and IL-13-mediated production of reactive oxygen species and subsequent POSTN upregulation in dermal fibroblasts. In contrast, NRF2 silencing abolished the cinnamaldehyde-mediated downregulation of POSTN. These results suggest that cinnamaldehyde is a broad inhibitor of POSTN expression covering both TGF-β1 and IL-13 signaling. Cinnamaldehyde may thus be beneficial for the treatment of systemic fibrotic diseases.

scholarly journals Thrombopoietin/TGF-β1 Loop Regulates Megakaryocyte Extracellular Matrix Component Synthesis

Stem Cells ◽  
2016 ◽  
Vol 34 (4) ◽  
pp. 1123-1133 ◽  
Author(s):  
Vittorio Abbonante ◽  
Christian A. Di Buduo ◽  
Cristian Gruppi ◽  
Alessandro Malara ◽  
Umberto Gianelli ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Extracellular Matrix Component ◽  
Matrix Component ◽  
Tgf Β1

scholarly journals Single-cell RNA-seq reveals fibroblast heterogeneity and increased mesenchymal fibroblasts in human fibrotic skin diseases

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Cheng-Cheng Deng ◽  
Yong-Fei Hu ◽  
Ding-Heng Zhu ◽  
Qing Cheng ◽  
Jing-Jing Gu ◽  
...  
Keyword(s):  
Single Cell ◽  
Skin Disease ◽  
Skin Diseases ◽  
Rna Seq ◽  
Fibrotic Disease ◽  
Functional Studies ◽  
Fibrotic Diseases ◽  
Fibroblast Heterogeneity ◽  
Keloid Fibroblasts ◽  
Excessive Accumulation

AbstractFibrotic skin disease represents a major global healthcare burden, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix. Fibroblasts are found to be heterogeneous in multiple fibrotic diseases, but fibroblast heterogeneity in fibrotic skin diseases is not well characterized. In this study, we explore fibroblast heterogeneity in keloid, a paradigm of fibrotic skin diseases, by using single-cell RNA-seq. Our results indicate that keloid fibroblasts can be divided into 4 subpopulations: secretory-papillary, secretory-reticular, mesenchymal and pro-inflammatory. Interestingly, the percentage of mesenchymal fibroblast subpopulation is significantly increased in keloid compared to normal scar. Functional studies indicate that mesenchymal fibroblasts are crucial for collagen overexpression in keloid. Increased mesenchymal fibroblast subpopulation is also found in another fibrotic skin disease, scleroderma, suggesting this is a broad mechanism for skin fibrosis. These findings will help us better understand skin fibrotic pathogenesis, and provide potential targets for fibrotic disease therapies.

scholarly journals Galvanic microparticles increase migration of human dermal fibroblasts in a wound-healing model via reactive oxygen species pathway

2014 ◽  
Vol 320 (1) ◽  
pp. 79-91 ◽  
Author(s):  
Nina Tandon ◽  
Elisa Cimetta ◽  
Aranzazu Villasante ◽  
Nicolette Kupferstein ◽  
Michael D. Southall ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Wound Healing ◽  
Reactive Oxygen ◽  
Dermal Fibroblasts ◽  
Oxygen Species ◽  
Human Dermal Fibroblasts ◽  
Wound Healing Model ◽  
Healing Model

scholarly journals Hyperglycaemia and aberrated insulin signalling stimulate tumour progression via induction of the extracellular matrix component hyaluronan

2017 ◽  
Vol 141 (4) ◽  
pp. 791-804 ◽  
Author(s):  
Sören Twarock ◽  
Christina Reichert ◽  
Ulrike Peters ◽  
Daniel J. Gorski ◽  
Katharina Röck ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Insulin Signalling ◽  
Tumour Progression ◽  
Extracellular Matrix Component ◽  
Matrix Component

scholarly journals Expression of extracellular matrix molecules in human mesangial cells in response to prolonged hyperglycaemia

1996 ◽  
Vol 316 (3) ◽  
pp. 985-992 ◽  
Author(s):  
Nadia Abdel WAHAB ◽  
Katherine HARPER ◽  
Roger M. MASON
Keyword(s):  
Cell Cultures ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Dermal Fibroblasts ◽  
Rt Pcr ◽  
Collagen Types ◽  
Human Mesangial Cells ◽  
Core Proteins ◽  
Cell Layers ◽  
Tgf Β1

Post-mitotic cultures of human mesangial cells were maintained in media containing 4–30 mM D-glucose for up to 28 days. Changes in mRNA and protein levels for specific macromolecules occurred between 7 and 14 days after initiating hyperglycaemic conditions. Slot blot analysis showed 2–3-fold increases in mRNAs for collagen type I, fibronectin, versican and perlecan, whereas mRNA for decorin was increased by up to 20-fold. Levels of mRNAs for biglycan and syndecan were unaffected by hyperglycaemic culture. Reverse transcriptase PCR (RT–PCR) confirmed that decorin mRNA levels are greatly elevated and also showed increased transcription of the TGF-β1 gene in hyperglycaemic cultures. Western analysis and ELISA indicated accumulations of collagen types I and III, laminin and fibronectin in the cell layers and media of hyperglycaemic cultures with increasing time. Type IV collagen did not accumulate in either compartment of hyperglycaemic mesangial cell cultures. Collagen types I, III, and fibronectin did not accumulate in the cell layers of hyperglycaemic human dermal fibroblasts, indicating a cell-specific response in mesangial cultures. Decorin and versican, but not biglycan, were increased in the hyperglycaemic mesangial cell culture media. There were no apparent changes in core proteins for decorin and biglycan in fibroblast media. Transforming growth factor β1 (TGF-β1) in hyperglycaemic mesangial cell cultures increased 5-fold after 7 days, but decreased thereafter to only approx. 2-fold after 28 days. The changes in TGF-β1 mRNA, as detected by RT–PCR, and protein followed one another closely.

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