scholarly journals The HIPPO Transducer YAP and Its Targets CTGF and Cyr61 Drive a Paracrine Signalling in Cold Atmospheric Plasma-Mediated Wound Healing

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Debarati Shome ◽  
Thomas von Woedtke ◽  
Katharina Riedel ◽  
Kai Masur

Reactive species play a pivotal role in orchestrating wound healing responses. They act as secondary messengers and drive redox-signalling pathways that are involved in the homeostatic, inflammatory, proliferative, and remodelling phases of wound healing. The application of Cold Atmospheric Plasma (CAP) to the wound site produces a profusion of short- and long-lived reactive species that have been demonstrated to be effective in promoting wound healing; however, knowledge of the mechanisms underlying CAP-mediated wound healing remains scarce. To address this, an in vitro coculture model was used to study the effects of CAP on wound healing and on paracrine crosstalk between dermal keratinocytes and fibroblasts. Using this coculture model, we observed a stimulatory effect on the migration ability of HaCaT cells that were cocultured with dermal fibroblasts. Additionally, CAP treatment resulted in an upregulation of the HIPPO transcription factor YAP in HaCaTs and fibroblasts. Downstream effectors of the HIPPO signalling pathway (CTGF and Cyr61) were also upregulated in dermal fibroblasts, and the administration of antioxidants could inhibit CAP-mediated wound healing and abrogate the gene expression of the HIPPO downstream effectors. Interestingly, we observed that HaCaT cells exhibited an improved cell migration rate when incubated with CAP-treated fibroblast-conditioned media compared to that observed after incubation with untreated media. An induction of CTGF and Cyr61 secretion was also observed upon CAP treatment in the fibroblast-conditioned media. Finally, exposure to recombinant CTGF and Cyr61 could also significantly improve HaCaT cell migration. In summary, our results validated that CAP activates a regenerative signalling pathway at the onset of wound healing. Additionally, CAP also stimulated a reciprocal communication between dermal fibroblasts and keratinocytes, resulting in improved keratinocyte wound healing in coculture.

2010 ◽  
Vol 299 (2) ◽  
pp. C528-C534 ◽  
Author(s):  
Chih-Chin Hsu ◽  
Wen-Chung Tsai ◽  
Carl Pai-Chu Chen ◽  
Yun-Mei Lu ◽  
Jong-Shyan Wang

Negative-pressure wound therapy has recently gained popularity in chronic wound care. This study attempted to explore effects of different negative pressures on epithelial migration in the wound-healing process. The electric cell-substrate impedance sensing (ECIS) technique was used to create a 5 × 10−4 cm2 wound in the Madin-Darby canine kidney (MDCK) and human keratinocyte (HaCaT) cells. The wounded cells were cultured in a negative pressure incubator at ambient pressure (AP) and negative pressures of 75 mmHg (NP75), 125 mmHg (NP125), and 175 mmHg (NP175). The effective time (ET), complete wound healing time ( Tmax), healing rate ( Rheal), cell diameter, and wound area over time at different pressures were evaluated. Traditional wound-healing assays were prepared for fluorescent staining of cells viability, cell junction proteins, including ZO-1 and E-cadherin, and actins. Amount of cell junction proteins at AP and NP125 was also quantified. In MDCK cells, the ET (1.25 ± 0.27 h), Tmax (1.76 ± 0.32 h), and Rheal (2.94 ± 0.62 × 10−4 cm2/h) at NP125 were significantly ( P < 0.01) different from those at three other pressure conditions. In HaCaT cells, the Tmax (7.34 ± 0.29 h) and Rheal (6.82 ± 0.26 × 10−5 cm2/h) at NP125 were significantly ( P < 0.01) different from those at NP75. Prominent cell migration features were identified in cells at the specific negative pressure. Cell migration activities at different pressures can be documented with the real-time wound-healing measurement system. Negative pressure of 125 mmHg can help disassemble the cell junction to enhance epithelial migration and subsequently result in quick wound closure.


2019 ◽  
Vol 47 (11) ◽  
pp. 4848-4860 ◽  
Author(s):  
Donghai Li ◽  
Guiling Li ◽  
Jing Li ◽  
Zhi-Qiang Liu ◽  
Xuman Zhang ◽  
...  

2018 ◽  
Vol 8 (4) ◽  
pp. 379-401 ◽  
Author(s):  
Constance Duchesne ◽  
Nadira Frescaline ◽  
Jean-Jacques Lataillade ◽  
Antoine Rousseau

2020 ◽  
Vol 5 (10) ◽  

Cold atmospheric plasma (CAP), a room temperate ionised gas, known as the fourth state of matter is an ionised gas and can be produced from argon, helium, nitrogen, oxygen or air at atmospheric pressure and low temperatures. CAP has become a new promising way for many biomedical applications, such as disinfection, cancer treatment, root canal treatment, wound healing, and other medical applications. Among these applications, investigations of plasma for skin wound healing have gained huge success both in vitro and in vivo experiments without any known significant negative effects on healthy tissues. The development of CAP devices has led to novel therapeutic strategies in wound healing, tissue regeneration and skin infection management. CAP consists of a mixture of multitude of active components such as charged particles, electric field, UV radiation, and reactive gas species which can act synergistically. CAP has lately been recognized as an alternative approach in medicine for sterilization of wounds by its antiseptic effects and promotion of wound healing by stimulation of cell proliferation and migration of wound related skin cells. With respect to CAP applications in medicine, this review focuses particularly on the potential of CAP and the known molecular basis for this action. We summarize the available literature on the plasma devices developed for wound healing, the current in vivo and in vitro use of CAP, and the mechanism behind it as well as the biosafety issues.


2019 ◽  
Vol 2019 ◽  
pp. 1-21 ◽  
Author(s):  
Christian Scharf ◽  
Christine Eymann ◽  
Philipp Emicke ◽  
Jörg Bernhardt ◽  
Martin Wilhelm ◽  
...  

The promising potential of cold atmospheric plasma (CAP) treatment as a new therapeutic option in the field of medicine, particularly in Otorhinolaryngology and Respiratory medicine, demands primarily the assessment of potential risks and the prevention of any direct and future cell damages. Consequently, the application of a special intensity of CAP that is well tolerated by cells and tissues is of particular interest. Although improvement of wound healing by CAP treatment has been described, the underlying mechanisms and the molecular influences on human tissues are so far only partially characterized. In this study, human S9 bronchial epithelial cells were treated with cold plasma of atmospheric pressure plasma jet that was previously proven to accelerate the wound healing in a clinically relevant extent. We studied the detailed cellular adaptation reactions for a specified plasma intensity by time-resolved comparative proteome analyses of plasma treated vs. nontreated cells to elucidate the mechanisms of the observed improved wound healing and to define potential biomarkers and networks for the evaluation of plasma effects on human epithelial cells. K-means cluster analysis and time-related analysis of fold-change factors indicated concordantly clear differences between the short-term (up to 1 h) and long-term (24-72 h) adaptation reactions. Thus, the induction of Nrf2-mediated oxidative and endoplasmic reticulum stress response, PPAR-alpha/RXR activation as well as production of peroxisomes, and prevention of apoptosis already during the first hour after CAP treatment are important cell strategies to overcome oxidative stress and to protect and maintain cell integrity and especially microtubule dynamics. After resolving of stress, when stress adaptation was accomplished, the cells seem to start again with proliferation and cellular assembly and organization. The observed strategies and identification of marker proteins might explain the accelerated wound healing induced by CAP, and these indicators might be subsequently used for risk assessment and quality management of application of nonthermal plasma sources in clinical settings.


2019 ◽  
Vol 17 (2) ◽  
pp. 1900103 ◽  
Author(s):  
Marina A. Pranda ◽  
Brittney J. Murugesan ◽  
Andrew J. Knoll ◽  
Gottlieb S. Oehrlein ◽  
Kimberly M. Stroka

2018 ◽  
Vol 59 (1) ◽  
pp. 92-101 ◽  
Author(s):  
Jun-Ping Zhang ◽  
Ling Guo ◽  
Qi-Liang Chen ◽  
Ke-Ying Zhang ◽  
Tian Wang ◽  
...  

RSC Advances ◽  
2016 ◽  
Vol 6 (82) ◽  
pp. 78457-78467 ◽  
Author(s):  
Fanny Girard ◽  
Vasilica Badets ◽  
Sylvie Blanc ◽  
Kristaq Gazeli ◽  
Laurent Marlin ◽  
...  

Cold Atmospheric Plasmas (CAPs) are increasingly used for biomedical applications, their various reactive components must be then better determined. We demonstrate that peroxynitrite (ONOO−) is effectively a major reactive species generated by CAPs.


Sign in / Sign up

Export Citation Format

Share Document