Molecular Changes Underlying Hypertrophic Scarring Following Burns Involve Specific Deregulations at All Wound Healing Stages (Inflammation, Proliferation and Maturation)

Čoma, Matúš; Fröhlichová, Lucia; Urban, Lukáš; Zajíček, Robert; Urban, Tomáš; Szabó, Pavol; Novák, S; Fetissov, Vitaly; Dvořánková, Barbora; Smetana, Karel; Gál, Péter

doi:10.3390/ijms22020897

Cited by 44 publications

(48 citation statements)

References 185 publications

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“…It is conceivable that the ILK/Akt pathway may regulate proliferation and survival of various types of abnormal fibroblasts and may be promising for prevention and treatment of fibrosis. Abnormal activation of fibroblasts in wounds has been reported to lead to the occurrence of pathological repair [ 44 , 45 ]. This perspective is supported by our data, as we found that compared with normal airway fibroblasts, the ILK/Akt pathway was abnormally activated in PHAGF, leading to stronger proliferative activity and anti-apoptotic ability, and β-elemene suppressed the viability of PHAGF by attenuating its ILK/Akt pathway.…”

Section: Discussionmentioning

confidence: 99%

β-elemene alleviates airway stenosis via the ILK/Akt pathway modulated by MIR143HG sponging miR-1275

2021

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Background We have previously found that β-elemene could inhibit the viability of airway granulation fibroblasts and prevent airway hyperplastic stenosis. This study aimed to elucidate the underlying mechanism and protective efficacy of β-elemene in vitro and in vivo. Methods Microarray and bioinformatic analysis were used to identify altered pathways related to cell viability in a β-elemene-treated primary cell model and to construct a β-elemene-altered ceRNA network modulating the target pathway. Loss of function and gain of function approaches were performed to examine the role of the ceRNA axis in β-elemene's regulation of the target pathway and cell viability. Additionally, in a β-elemene-treated rabbit model of airway stenosis, endoscopic and histological examinations were used to evaluate its therapeutic efficacy and further verify its mechanism of action. Results The hyperactive ILK/Akt pathway and dysregulated LncRNA-MIR143HG, which acted as a miR-1275 ceRNA to modulate ILK expression, were suppressed in β-elemene-treated airway granulation fibroblasts; β-elemene suppressed the ILK/Akt pathway via the MIR143HG/miR-1275/ILK axis. Additionally, the cell cycle and apoptotic phenotypes of granulation fibroblasts were altered, consistent with ILK/Akt pathway activity. In vivo application of β-elemene attenuated airway granulation hyperplasia and alleviated scar stricture, and histological detections suggested that β-elemene's effects on the MIR143HG/miR-1275/ILK axis and ILK/Akt pathway were in line with in vitro findings. Conclusions MIR143HG and ILK may act as ceRNA to sponge miR-1275. The MIR143HG/miR-1275/ILK axis mediates β-elemene-induced cell cycle arrest and apoptosis of airway granulation fibroblasts by modulating the ILK/Akt pathway, thereby inhibiting airway granulation proliferation and ultimately alleviating airway stenosis.

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Section: Discussionmentioning

confidence: 99%

β-elemene alleviates airway stenosis via the ILK/Akt pathway modulated by MIR143HG sponging miR-1275

2021

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“…Of note, this microenvironment represents a highly dynamic system. As cryotherapy represents the acute phase of wounding, its "healing" is associated with time-limited activation of immune system in order to remove tissue debris and minimize risk of infection [70]. This also establishes a new immune equilibrium and changes the tumour promoting setting of the cancer-associated microenvironment.…”

Section: Discussionmentioning

confidence: 99%

The Abscopal Effect in the Era of Checkpoint Inhibitors

Kodet

Němejcová

Strnadová

et al. 2021

IJMS

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Therapy targeting immune checkpoints represents an integral part of the treatment for patients suffering from advanced melanoma. However, the mechanisms of resistance are responsible for a lower therapeutic outcome than expected. Concerning melanoma, insufficient stimulation of the immune system by tumour neoantigens is a likely explanation. As shown previously, radiotherapy is a known option for increasing the production of tumour neoantigens and their release into the microenvironment. Consequently, neoantigens could be recognized by antigen presenting cells (APCs) and subjected to effector T lymphocytes. Enhancing the immune reaction can trigger the therapeutic response also at distant metastases, a phenomenon known as an abscopal effect (from “ab scopus”, that is, away from the target). To illustrate this, we present the case of a 78-year old male treated by anti-CTLA-4/ipilimumab for metastatic melanoma. The patient received the standard four doses of ipilimumab administered every three weeks. However, the control CT scans detected disease progression in the form of axillary lymph nodes metastasis and liver metastasis two months after ipilimumab. At this stage, palliative cryotherapy of the skin metastases was initiated to alleviate the tumour burden. Surprisingly, the effect of cryotherapy was also observed in untreated metastases and deep subcutaneous metastases on the back. Moreover, we observed the disease remission of axillary lymph nodes and liver metastasis two months after the cryotherapy. The rarity of the abscopal effect suggests that even primed anti-tumour CD8+ T cells cannot overcome the tumour microenvironment’s suppressive effect and execute immune clearance. However, the biological mechanism underlying this phenomenon is yet to be elucidated. The elicitation of a systemic response by cryotherapy with documented abscopal effect was rarely reported, although the immune response induction is presumably similar to a radiotherapy-induced one. The report is a combination case study and review of the abscopal effect in melanoma treated with checkpoint inhibitors.

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“…In the process of wound repair, angiogenesis is essential for the delivery of oxygen and nutrients to the newly developed tissue. Angiogenesis is comprised of consecutive actions including migration and proliferation of endothelial cells orchestrated by growth factors, oxygen levels, and proteases [2]. Recently, it was revealed that genistein can impact the growth and budding of endothelial cells, the formation of new capillaries, and some of the signaling pathways connected to angiogenesis [78] also via alteration of vascular endothelial growth factor (VEGF).…”

Section: Angiogeneismentioning

confidence: 99%

“…Wound healing is a dynamic event running in four basic phases, i.e., hemostasis, inflammation, proliferation, and maturation/remodeling, which overlap with each other in a consecutive manner restoring the disrupted integrity of tissues/organs. Immediately following blood clotting inflammatory/immune cells enter the injury site to eliminate pathogens and remove necrotic tissue [2]. Fibroblasts located in the granulation tissue excrete and remodel extracellular matrix (ECM) proteins, whereas differentiated myofibroblasts contract the wound [3].…”

Section: Introductionmentioning

confidence: 99%

Molecular Changes Underlying Genistein Treatment of Wound Healing: A Review

Čoma

Lachová

Mitrengová

et al. 2021

CIMB

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Estrogen deprivation is one of the major factors responsible for many age-related processes including poor wound healing in postmenopausal women. However, the reported side-effects of estrogen replacement therapy (ERT) have precluded broad clinical administration. Therefore, selective estrogen receptor modulators (SERMs) have been developed to overcome the detrimental side effects of ERT on breast and/or uterine tissues. The use of natural products isolated from plants (e.g., soy) may represent a promising source of biologically active compounds (e.g., genistein) as efficient alternatives to conventional treatment. Genistein as natural SERM has the unique ability to selectively act as agonist or antagonist in a tissue-specific manner, i.e., it improves skin repair and simultaneously exerts anti-cancer and chemopreventive properties. Hence, we present here a wound healing phases-based review of the most studied naturally occurring SERM.

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Molecular Changes Underlying Hypertrophic Scarring Following Burns Involve Specific Deregulations at All Wound Healing Stages (Inflammation, Proliferation and Maturation)

Cited by 44 publications

References 185 publications

β-elemene alleviates airway stenosis via the ILK/Akt pathway modulated by MIR143HG sponging miR-1275

β-elemene alleviates airway stenosis via the ILK/Akt pathway modulated by MIR143HG sponging miR-1275

The Abscopal Effect in the Era of Checkpoint Inhibitors

Molecular Changes Underlying Genistein Treatment of Wound Healing: A Review

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