The Involvement of SDF-1α/CXCR4 Axis in Radiation-Induced Acute Injury and Fibrosis of Skin

Cao, Jinming; Zhu, Wei; Yu, Daojiang; Pan, Lu; Zhong, Li; Xiao, Yuji; Gao, Yiying; Jiao, Yang; Zhang, Qi; Ji, Jiang; Yang, Huiling; Zhang, Shuyu; Cao, Jianping

doi:10.1667/rr15384.1

Cited by 13 publications

(9 citation statements)

References 37 publications

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“…At the same time, there was an increase of signals related with immune system activation, centered in the activation of the transcription of the cytokine Cxcl12, a potent chemoattractant for hematopoietic cells. This molecule has been associated to fibrosis after radiation injury (Cao et al, 2019) and also to pro-metastatic stimulus of colon cancer cells through the PI3K/AKT/mTOR signaling pathway (Ma et al, 2017). However, in massive liver injury models where oval cell repair is involved, there is an upregulation of Cxcl12 that interacts with oval cells because this cell type expresses CXCR4, the only known receptor for CXCL12 (Hatch et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles From Liver Progenitor Cells Downregulates Fibroblast Metabolic Activity and Increase the Expression of Immune-Response Related Molecules

Royo

Azkargorta

Lavín

et al. 2021

Front. Cell Dev. Biol.

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Extracellular vesicles (EVs) mediate cell-to-cell crosstalk whose content can induce changes in acceptor cells and their microenvironment. MLP29 cells are mouse liver progenitor cells that release EVs loaded with signaling cues that could affect cell fate. In the current work, we incubated 3T3-L1 mouse fibroblasts with MLP29-derived EVs, and then analyzed changes by proteomics and transcriptomics. Results showed a general downregulation of protein and transcript expression related to proliferative and metabolic routes dependent on TGF-beta. We also observed an increase in the ERBB2 interacting protein (ERBIN) and Cxcl2, together with an induction of ribosome biogenesis and interferon-related response molecules, suggesting the activation of immune system signaling.

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Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles From Liver Progenitor Cells Downregulates Fibroblast Metabolic Activity and Increase the Expression of Immune-Response Related Molecules

Royo

Azkargorta

Lavín

et al. 2021

Front. Cell Dev. Biol.

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“…A 3-cm-thick piece of lead was used to shield the animals and localize the radiation field (3×4 cm). Irradiation was administered to the treatment area at a dose rate of 750 cGy/min using a 6-MeV electron beam accelerator (Clinac 2100EX, Varian Medical Systems) as we reported previously (15)(16)(17)(18)(19)(20)(21)(22).…”

Section: Animal Studiesmentioning

confidence: 99%

“…No animals were excluded from analysis. Skin reactions were graded at regular intervals from 1 (no damage) to 5 (severe damage) using the semiquantitative skin injury scale as previously described (15)(16)(17)(18)(19)(20)(21)(22).…”

Section: Animal Studiesmentioning

confidence: 99%

NF-E2-Related Factor 2 (Nrf2) Ameliorates Radiation-Induced Skin Injury

Xue

Tang

et al. 2021

Front. Oncol.

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Radiation-induced skin injury (RISI) commonly occur in cancer patients who received radiotherapy and is one of the first clinical symptoms after suffering from nuclear exposure. Oxidative damage is the major causes of RISI. Nuclear factor erythroid 2-related factor 2 (Nrf2) is considered as a key mediator of the cellular antioxidant response. However, whether Nrf2 can alleviate RISI after high-dose irradiation remains unknown. In this study, we demonstrated that Nrf2-deficient (Nrf2-/-) mice were susceptible to high-dose irradiation and adenovirus-mediated overexpression of Nrf2 (ad-Nrf2) protected against radiation in skin cells. Overexpression of Nrf2 attenuated the severity of skin injury after high-dose electron beam irradiation. To uncover the mechanisms of Nrf2 involved in RISI, mRNA sequencing technology was performed to analyze the mRNA expression profiles of Ad-Nrf2 skin cells following radiation. The results revealed that a total of 127 genes were significantly changed, 55 genes were upregulated, and 72 genes were downregulated after Nrf2 overexpression. GSEA showed that Nrf2 was associated with positive regulation of genes involved in the reactive oxygen species pathway after radiation. Taken together, this study illustrated the role of Nrf2 in RISI and provided potentially strategies for ameliorating RISI.

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“…CXCL14 работает как хемоаттрактант для активированных макрофагов, незрелых дендритных клеток и NK-клеток, а также оказывает ингибиторный эффект на сигнальный путь CXCL12/CXCR4, который обеспечивает поддержание Th1-зависимого иммунного ответа в коже. Рецептор CXCR4 принимает участие в развитии фиброза кожи [16]. Снижение экспрессии CXCL14 способствует поддержанию поляризации иммунного ответа в сторону Th2, а также нарушает васкуляризацию в коже [17].…”

Section: оригинальная статьяunclassified

“…Рецепторы CCR3 и CXCR4, экспрессируемые на лимфоцитах, инициируют сигнальные пути, принимающие участие в развитии фиброза кожи [16,19]. В среднем при ожирении не было значимого повышения уровня этих рецепторов, однако при персонолизированном анализе результатов установлено, что у 5% пациенток с ожирением плотность этих рецепторов превышал норму в 2 раза.…”

Section: результаты исследованияunclassified

Levels of keratinocyteand fibroblast-derived chemokines in skin cells isolated from abdominoplasty surgical materials from patients with normal weight and obesity

Копасов¹,

Volkova²,

Blokhin³

et al. 2020

ZHurnal «Patologicheskaia Fiziologiia I Eksperimental`naia Terapiia»

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Цель работы - определение уровня хемокинов, ассоциированных с фибробластами и кератиноцитами, в клетках кожи, выделеных из операционного материала при абдоминопластике у пациенток с нормальной массой тела и ожирением. Методика. Для исследования использовали фрагменты кожи пациенток с нормальной массой тела и ожирением. Степень ожирения оценивали по индексу массы тела (ИМТ) согласно международным критериям. ИМТ, принятый в исследовании за норму, составлял 19,8±1,7 кг/м2, для пациенток с ожирением - 38,3±4,1 кг/м2. Клетки выделяли путем ферментативной обработки коллагеназой II. Проводили иммунотипирование клеток моноклональными антителами меченными флуоресцентными красителями. Использовали антитела к хемокинам семейства CXCL (R&D systems) и CCL (Boeringer Ingelheim, Германия). Меченные флуоресцентными красителями иммунотипированные клетки анализировали на проточном цитометре FACSCalibur (Becton Dickinson, США) по программе SimulSet. Статистический анализ проводили по программе ANOVA. Результаты. Были проанализированы хемокины семейства CCL и CXCL, секретируемые кератиноцитами и фибробластами кожи. Показано, что в коже пациенток с ожирением повышен процент клеток, экспрссирующих рецепторы CXCR3, CXCR4, CCR3, CCR10, регулирующие секрецию хемокинов кератиноцитами и фибробластами кожи. При ожирении в клетках кожи повышен уровень хемокинов CXCL8, CXCL9, CXCL10, CXCL13, CCL24 и CCL27, имеющих отношение к развитию и поддержанию воспалительного процесса в коже, а уровень хемокинов CCL17, CCL22, CCL28 снижен, что указывает на нарушение хемокиновой и цитокиновой регуляции при ожирении и является основой для развития послеоперационных осложнений при абдоминопластике. Заключение. Полученные данные указывают на нарушение хемокиновой регуляции при ожирении, что способствует развитию послеоперационных осложнений при абдоминопластике. The aim of the study was to compare chemokine expression in skin cells obtained from patients with normal body weight and obesity after abdominoplasty. Methods. Obesity was determined by body weight index (normal, 19.8±1.7 kg/m2; obesity, 38.3±4.1 kg/m2). Only skin without subcutaneous fat was isolated from surgical material. The skin cells obtained from surgical material were stained with monoclonal antibodies to chemokines. Fluorescence of proteins and receptors was analyzed by flow cytometry. Statistical analysis was performed with ANOVA. Results. Keratinocyte- and fibroblast-derived chemokines of the CCL and CXCL families were analyzed. Percentage of cells expressing CXCR3, CXCR4, CCR3, and CCR10 receptors (regulators of chemokine secretion by keratinocytes and skin fibroblasts) was increased in the skin of obese patients. Expression of the pro-inflammatory chemokines, CXCL8, CXCL9, CXCL10, CXCL13, CCL24, and CCL27, was increased in skin cells from obese patients. Obesity was associated with reduced expression of the chemokines CCL17, CCL22, and CCL28 in skin cells. Conclusion. Chemokine regulation is disturbed in obesity, which may underlie the development of complications after abdominal surgery.

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The Involvement of SDF-1α/CXCR4 Axis in Radiation-Induced Acute Injury and Fibrosis of Skin

Cited by 13 publications

References 37 publications

Extracellular Vesicles From Liver Progenitor Cells Downregulates Fibroblast Metabolic Activity and Increase the Expression of Immune-Response Related Molecules

Extracellular Vesicles From Liver Progenitor Cells Downregulates Fibroblast Metabolic Activity and Increase the Expression of Immune-Response Related Molecules

NF-E2-Related Factor 2 (Nrf2) Ameliorates Radiation-Induced Skin Injury

Levels of keratinocyteand fibroblast-derived chemokines in skin cells isolated from abdominoplasty surgical materials from patients with normal weight and obesity

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