scholarly journals Fibroblast-to-myofibroblast switch is mediated by NAD(P)H oxidase generated reactive oxygen species

2014 ◽  
Vol 34 (1) ◽  
Author(s):  
Lirija Alili ◽  
Maren Sack ◽  
Katharina Puschmann ◽  
Peter Brenneisen

Tumour–stroma interaction is a prerequisite for tumour progression in skin cancer. Hereby, a critical step in stromal function is the transition of tumour-associated fibroblasts to MFs (myofibroblasts) by growth factors, for example TGFβ (transforming growth factor beta(). In this study, the question was addressed of whether fibroblast-associated NAD(P)H oxidase (NADH/NADPH oxidase), known to be activated by TGFβ1, is involved in the fibroblast-to-MF switch. The up-regulation of αSMA (alpha smooth muscle actin), a biomarker for MFs, is mediated by a TGFβ1-dependent increase in the intracellular level of ROS (reactive oxygen species). This report demonstrates two novel aspects of the TGFβ1 signalling cascade, namely the generation of ROS due to a biphasic NAD(P)H oxidase activity and a ROS-dependent downstream activation of p38 leading to a transition of dermal fibroblasts to MFs that can be inhibited by the selective NAD(P)H oxidase inhibitor apocynin. These data suggest that inhibition of NAD(P)H oxidase activity prevents the fibroblast-to-MF switch and may be important for chemoprevention in context of a ‘stromal therapy’ which was described earlier.

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Lirija Alili ◽  
Swetlana Chapiro ◽  
Gernot U. Marten ◽  
Annette M. Schmidt ◽  
Klaus Zanger ◽  
...  

Iron oxide (Fe3O4) nanoparticles have been used in many biomedical approaches. The toxicity of Fe3O4nanoparticles on mammalian cells was published recently. Though, little is known about the viability of human cells after treatment with Fe3O4nanoparticles. Herein, we examined the toxicity, production of reactive oxygen species, and invasive capacity after treatment of human dermal fibroblasts (HDF) and cells of the squamous tumor cell line (SCL-1) with Fe3O4nanoparticles. These nanoparticles had an average size of 65 nm. Fe3O4nanoparticles induced oxidative stress via generation of reactive oxygen species (ROS) and subsequent initiation of lipid peroxidation. Furthermore, the question was addressed of whether Fe3O4nanoparticles affect myofibroblast formation, known to be involved in tumor invasion. Herein, Fe3O4nanoparticles prevent the expression alpha-smooth muscle actin and therefore decrease the number of myofibroblastic cells. Moreover, our data showin vitrothat concentrations of Fe3O4nanoparticles, which are nontoxic for normal cells, partially reveal a ROS-triggered cytotoxic but also a pro-invasive effect on the fraction of squamous cancer cells surviving the treatment with Fe3O4nanoparticles. The data herein show that the Fe3O4nanoparticles appear not to be adequate for use in therapeutic approaches against cancer cells, in contrast to recently published data with cerium oxide nanoparticles.


Marine Drugs ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. 163
Author(s):  
Eleonora Binatti ◽  
Gianni Zoccatelli ◽  
Francesca Zanoni ◽  
Giulia Donà ◽  
Federica Mainente ◽  
...  

Radiation-induced fibrosis is a serious long-lasting side effect of radiation therapy. Central to this condition is the role of macrophages that, activated by radiation-induced reactive oxygen species and tissue cell damage, produce pro-inflammatory cytokines, such as transforming growth factor beta (TGFβ). This, in turn, recruits fibroblasts at the site of the lesion that initiates fibrosis. We investigated whether astaxanthin, an antioxidant molecule extracted from marine and freshwater organisms, could help control macrophage activation. To this purpose, we encapsulated food-grade astaxanthin from Haematococcus pluvialis into micrometer-sized whey protein particles to specifically target macrophages that can uptake material within this size range by phagocytosis. The data show that astaxanthin-loaded microparticles are resistant to radiation, are well-tolerated by J774A.1 macrophages, induce in these cells a significant reduction of intracellular reactive oxygen species and inhibit the release of active TGFβ as evaluated in a bioassay with transformed MFB-F11 fibroblasts. Micro-encapsulation of bioactive molecules is a promising strategy to specifically target phagocytic cells and modulate their own functions.


Biochimie ◽  
2007 ◽  
Vol 89 (12) ◽  
pp. 1464-1473 ◽  
Author(s):  
Dalliah Black ◽  
Suzanne Lyman ◽  
Ting Qian ◽  
John J. Lemasters ◽  
Richard A. Rippe ◽  
...  

2014 ◽  
Vol 320 (1) ◽  
pp. 79-91 ◽  
Author(s):  
Nina Tandon ◽  
Elisa Cimetta ◽  
Aranzazu Villasante ◽  
Nicolette Kupferstein ◽  
Michael D. Southall ◽  
...  

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