Connexin-dependent intercellular stress signaling in tissue homeostasis and tumor development

Czyż, Jarosław; Piwowarczyk, Katarzyna; Paw, Milena; Luty, Marcin; Wróbel, Tomasz; Catapano, Jessica; Madeja, Zbigniew; Ryszawy, Damian

doi:10.18388/abp.2017_1592

Cited by 17 publications

(16 citation statements)

References 176 publications

(213 reference statements)

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“…After stimulation, AS HBFs exhibited different expression patterns of some proteins compared to NA HBFs. The most important and notable differences are amplified levels of α-SMA and connexin (Cx) 43 (protein involved in the intercellular transfer of small metabolites and ions via hexameric channels termed gap junctions) [ 236 , 237 ] in response to TGF-β administration in AS HBFs compared to NA HBFs (Fig. 1 —upregulation of α-SMA and Cx43) [ 46 , 223 , 234 , 238 ].…”

Section: Fibroblast Featuresmentioning

confidence: 99%

Fibroblast-to-myofibroblast transition in bronchial asthma

Michalik

Wójcik-Pszczoła

Paw

et al. 2018

Cell. Mol. Life Sci.

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122

118

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Bronchial asthma is a chronic inflammatory disease in which bronchial wall remodelling plays a significant role. This phenomenon is related to enhanced proliferation of airway smooth muscle cells, elevated extracellular matrix protein secretion and an increased number of myofibroblasts. Phenotypic fibroblast-to-myofibroblast transition represents one of the primary mechanisms by which myofibroblasts arise in fibrotic lung tissue. Fibroblast-to-myofibroblast transition requires a combination of several types of factors, the most important of which are divided into humoural and mechanical factors, as well as certain extracellular matrix proteins. Despite intensive research on the nature of this process, its underlying mechanisms during bronchial airway wall remodelling in asthma are not yet fully clarified. This review focuses on what is known about the nature of fibroblast-to-myofibroblast transition in asthma. We aim to consider possible mechanisms and conditions that may play an important role in fibroblast-to-myofibroblast transition but have not yet been discussed in this context. Recent studies have shown that some inherent and previously undescribed features of fibroblasts can also play a significant role in fibroblast-to-myofibroblast transition. Differences observed between asthmatic and non-asthmatic bronchial fibroblasts (e.g., response to transforming growth factor β, cell shape, elasticity, and protein expression profile) may have a crucial influence on this phenomenon. An accurate understanding and recognition of all factors affecting fibroblast-to-myofibroblast transition might provide an opportunity to discover efficient methods of counteracting this phenomenon.

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Section: Fibroblast Featuresmentioning

confidence: 99%

Fibroblast-to-myofibroblast transition in bronchial asthma

Michalik

Wójcik-Pszczoła

Paw

et al. 2018

Cell. Mol. Life Sci.

Self Cite

122

118

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“…Furthermore, the upregulation of Cx43 levels observed in HBFs upon treatment of TGF-β 1 was significantly and dose-dependently reduced by fenofibrate. Cx43 regulates cellular processes in two different ways: gap junctional intercellular coupling (GJIC)-dependent and GJIC-independent methods [ 48 , 49 , 50 ]. We previously showed GJIC-independent associations between TGF-β 1 /Smad2 signaling and TGF-β 1 -induced FMT and Cx43 function in HBFs [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Fenofibrate Reduces the Asthma-Related Fibroblast-To-Myofibroblast Transition by TGF-Β/Smad2/3 Signaling Attenuation and Connexin 43-Dependent Phenotype Destabilization

Paw

Wnuk

Kądziołka

et al. 2018

IJMS

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The activation of human bronchial fibroblasts by transforming growth factor-β1 (TGF-β1) leads to the formation of highly contractile myofibroblasts in the process of the fibroblast–myofibroblast transition (FMT). This process is crucial for subepithelial fibrosis and bronchial wall remodeling in asthma. However, this process evades current therapeutic asthma treatment strategies. Since our previous studies showed the attenuation of the TGF-β1-induced FMT in response to lipid-lowering agents (e.g., statins), we were interested to see whether a corresponding effect could be obtained upon administration of hypolipidemic agents. In this study, we investigated the effect of fenofibrate on FMT efficiency in populations of bronchial fibroblasts derived from asthmatic patients. Fenofibrate exerted a dose-dependent inhibitory effect on the FMT, even though it did not efficiently affect the expression of α-smooth muscle actin (α-SMA; marker of myofibroblasts); however, it considerably reduced its incorporation into stress fibers through connexin 43 regulation. This effect was accompanied by disturbances in the actin cytoskeleton architecture, impairments in the maturation of focal adhesions, and the fenofibrate-induced deactivation of TGF-β1/Smad2/3 signaling. These data suggest that fenofibrate interferes with myofibroblastic differentiation during asthma-related subepithelial fibrosis. The data indicate the potential application of fenofibrate in the therapy and prevention of bronchial remodeling during the asthmatic process.

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“…Different expression patterns of the oxidative stress-regulating enzymes may be one of the reason of diminished level of intracellular ROS in KJT23I cells exposed to IONPs and Fe salts. On the other hand, it is worth emphasizing that KJT23I cells grow in colonies which provide close intercellular communication and the possibility of collective response and attenuation of Fe induced cytotoxicity (by-stander effect) 70 . A quite worrying phenomenon is the strong effect of iron in both forms on ROS production in kidney HEK293T cells.…”

Section: Discussionmentioning

confidence: 99%

Comparison of ultrasmall IONPs and Fe salts biocompatibility and activity in multi-cellular in vitro models

Janik-Olchawa

Dróżdż

Ryszawy

et al. 2020

Sci Rep

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In the paper, the results of the first regular studies of ultra-small iron oxide nanoparticles (IONPs) toxicity in vitro were presented. The influence of PEG-coated NPs with 5 nm magnetite core on six different cell lines was examined. These were: human bronchial fibroblasts, human embryonic kidney cells (HEK293T), two glioblastoma multiforme (GBM) cell lines as well as GBM cells isolated from a brain tumor of patient. Additionally, mouse macrophages were included in the study. The influence of IONPs in three different doses (1, 5 and 25 µg Fe/ml) on the viability, proliferation and migration activity of cells was assessed. Moreover, quantifying the intracellular ROS production, we determined the level of oxidative stress in cells exposed to IONPs. In the paper, for the first time, the effect of Fe in the form of IONPs was compared with the analogical data obtained for iron salts solutions containing the same amount of Fe, on the similar oxidation state. Our results clearly showed that the influence of iron on the living cells strongly depends not only on the used cell line, dose and exposure time but also on the form in which this element was administered to the culture. Notably, nanoparticles can stimulate the proliferation of some cell lines, including glioblastoma multiforme. Compared to Fe salts, they have a stronger negative impact on the viability of the cells tested. Ultra-small NPs, also, more often positively affect cell motility which seem to differ them from the NPs with larger core diameters.

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Connexin-dependent intercellular stress signaling in tissue homeostasis and tumor development

Cited by 17 publications

References 176 publications

Fibroblast-to-myofibroblast transition in bronchial asthma

Fibroblast-to-myofibroblast transition in bronchial asthma

Fenofibrate Reduces the Asthma-Related Fibroblast-To-Myofibroblast Transition by TGF-Β/Smad2/3 Signaling Attenuation and Connexin 43-Dependent Phenotype Destabilization

Comparison of ultrasmall IONPs and Fe salts biocompatibility and activity in multi-cellular in vitro models

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