Bone marrow mesenchymal stem cell‐conditioned medium facilitates fluid resolution via miR‐214‐activating epithelial sodium channels

Ding, Yan; Cui, Yong; Hou, Yapeng; Nie, Hongguang

doi:10.1002/mco2.40

Cited by 5 publications

(3 citation statements)

References 62 publications

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“…Furthermore, miRNAs can be secreted into body fluids, including blood, urine, cerebrospinal fluid, or saliva, which are called circulating miRNAs (Mitchell et al, 2008;Kosaka et al, 2010). It has been widely demonstrated that circulating miRNAs have potential to be used as diagnostic and/ or prognostic biomarkers or playing other functions in cancer (Mitchell et al, 2008;Ding et al, 2020). For example, circulating miR-1268b and miR-6075 in serum were identified as diagnostic markers of lung cancer (Asakura et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

A circulating miR-19b-based model in diagnosis of human breast cancer

Zhao

Shen

et al. 2022

Front. Mol. Biosci.

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Objective: Breast cancer (BC) is becoming the leading cause of cancer-related death in women all over the word. Identification of diagnostic biomarkers for early detection of BC is one of the most effective ways to reduce the mortality.Methods: Plasma samples from BC patients (n = 120) and normal controls (n = 50) were collected to determine the differentially expressed circulating miRNAs in BC patients. Binary logistic regression was applied to develop miRNA diagnostic models. Receiver operating characteristic (ROC) curves were applied to calculate the area under the curve (AUC). MMTV-PYMT mammary tumor mice were used to validate the expression change of those circulating miRNAs. Plasma samples from patients with other tumor types were collected to determine the specificity of the model in diagnosis of BC.Results: In the screening phase, 5 circulating miRNAs (miR-16, miR-17, miR-19b, miR-27a, and miR-106a) were identified as the most significantly upregulated miRNAs in plasma of BC patients. In consistence, the 5 miRNAs showed upregulation in the circulation of additional 80 BC patients in a tumor stagedependent manner. Application of a tumor-burden mice model further confirmed upregulation of the 5 miRNAs in circulation. Based on these data, five models with diagnostic potential of BC were developed. Among the 5 miRNAs, miR-19b ranked at the top position with the highest specificity and the biggest contribution. In combination with miR-16 and miR-106a, a miR-19b-based 3-circulating miRNA model was selected as the best for further validation. Taken the samples together, the model showed 92% of sensitivity and 90% of specificity in diagnosis of BC. In addition, three other tumor types including prostate cancer, thyroid cancer and colorectal cancer further verified the specificity of the BC diagnostic model. Conclusion:The current study developed a miR-19b-based 3-miRNA model holding potential for diagnosis of BC using blood samples.

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Section: Introductionmentioning

confidence: 99%

A circulating miR-19b-based model in diagnosis of human breast cancer

Zhao

Shen

et al. 2022

Front. Mol. Biosci.

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“…The slices were stained with hematoxylin and eosin (H&E) for microscopic examination. The lung injury score in each field was quantified according to previous reports [ 32 , 33 ].…”

Section: Methodsmentioning

confidence: 99%

Sustained induction of IP-10 by MRP8/14 via the IFNβ–IRF7 axis in macrophages exaggerates lung injury in endotoxemic mice

Wang,

Chen,

et al. 2023

Burns &Amp; Trauma

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Background As a damage-associated molecular pattern, the myeloid-related protein 8/14 (MRP8/14) heterodimer mediates various inflammatory diseases, such as sepsis. However, how MRP8/14 promotes lung injury by regulating the inflammatory response during endotoxemia remains largely unknown. This study aims at illuminating the pathological functions of MRP8/14 in endotoxemia. Methods An endotoxemic model was prepared with wild-type and myeloid cell-specific Mrp8 deletion (Mrp8ΔMC) mice for evaluating plasma cytokine levels. Lung injury was evaluated by hematoxylin and eosin (H&E) staining, injury scoring and wet-to-dry weight (W/D) ratio. The dynamic profile of interferon γ (IFNγ)-inducible protein 10 (IP-10) mRNA expression induced by macrophage MRP8/14 was determined by quantitative real-time polymerase chain reaction (qPCR). Immunoblotting was used to evaluate the increase in IP-10 level induced by activation of the JAK–STAT signaling pathway. Luciferase reporter assay was performed to detect the involvement of IRF7 in Ip-10 gene transcription. In vivo air pouch experiments were performed to determine the biological function of IP-10 induced by MRP8/14. Results Experiments with Mrp8ΔMC mice showed that MRP8/14 promoted the production of cytokines, including IP-10, in the bronchoalveolar lavage fluid (BALF) and lung injury in endotoxic mice. The result of qPCR showed sustained expression of Ip-10 mRNA in macrophages after treatment with MRP8/14 for 12 h. Neutralization experiments showed that the MRP8/14-induced Ip-10 expression in RAW264.7 cells was mediated by extracellular IFNβ. Western blotting with phosphorylation-specific antibodies showed that the JAK1/TYK2-STAT1 signaling pathway was activated in MRP8/14-treated RAW264.7 cells, leading to the upregulation of Ip-10 gene expression. IRF7 was further identified as a downstream regulator of the JAK–STAT pathway that mediated Ip-10 gene expression in macrophages treated with MRP8/14. In vivo air pouch experiments confirmed that the IFNβ-JAK1/TYK2-STAT1-IRF7 pathway was required for chemokine (C-X-C motif) receptor 3 (CXCR3)+ T lymphocyte migration, which promoted lung injury in the context of endotoxemia. Conclusions In summary, our study demonstrates that MRP8/14 induces sustained production of IP-10 via the IFNβ-JAK1/TYK2-STAT1-IRF7 pathway to attract CXCR3+ T lymphocytes into lung tissues and ultimately results in lung injury by an excessive inflammatory response in the context of endotoxemia.

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“…For instance, in studies published by Goolaerts et It is well known that the typical pathophysiological features of ALI are lung inflammation, changes in alveolar ion transport, and increased endothelial permeability, often resulting in acute respiratory distress syndrome (ARDS). In all the mentioned research, the administration of MSC-CM resulted in a reduction in lung tissue inflammation and enhancement in wound healing, mainly through activating alveolar macrophage (AM) function; the reduced expression of anti-apoptotic molecules accompanied by increased neutrophil apoptosis; the increased expression of miR-214 and miR-34c; and the downregulation of proinflammatory cytokines, such as IL-1β, IL-6, and TNF-α [62,75,77,[84][85][86]. A similar affirmative result was published by Su et al, who found out that CM obtained from induced pluripotent stem cells (iPSCs) can attenuate endotoxin-induced ALI on mice model via the significant enhancement of endogenous leukemia inhibitory factor production and a decrease in the transendothelial migration of neutrophils [87].…”

Section: Immunomodulating Properties Of Conditioned Media (Cm)mentioning

confidence: 99%

The Immunomodulatory Role of Cell-Free Approaches in SARS-CoV-2-Induced Cytokine Storm—A Powerful Therapeutic Tool for COVID-19 Patients

et al. 2023

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Currently, there is still no effective and definitive cure for the coronavirus disease 2019 (COVID-19) caused by the infection of the novel highly contagious severe acute respiratory syndrome virus (SARS-CoV-2), whose sudden outbreak was recorded for the first time in China in late December 2019. Soon after, COVID-19 affected not only the vast majority of China’s population but the whole world and caused a global health public crisis as a new pandemic. It is well known that viral infection can cause acute respiratory distress syndrome (ARDS) and, in severe cases, can even be lethal. Behind the inflammatory process lies the so-called cytokine storm (CS), which activates various inflammatory cytokines that damage numerous organ tissues. Since the first outbreak of SARS-CoV-2, various research groups have been intensively trying to investigate the best treatment options; however, only limited outcomes have been achieved. One of the most promising strategies represents using either stem cells, such as mesenchymal stem cells (MSCs)/induced pluripotent stem cells (iPSCs), or, more recently, using cell-free approaches involving conditioned media (CMs) and their content, such as extracellular vesicles (EVs) (e.g., exosomes or miRNAs) derived from stem cells. As key mediators of intracellular communication, exosomes carry a cocktail of different molecules with anti-inflammatory effects and immunomodulatory capacity. Our comprehensive review outlines the complex inflammatory process responsible for the CS, summarizes the present results of cell-free-based pre-clinical and clinical studies for COVID-19 treatment, and discusses their future perspectives for therapeutic applications.

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Bone marrow mesenchymal stem cell‐conditioned medium facilitates fluid resolution via miR‐214‐activating epithelial sodium channels

Cited by 5 publications

References 62 publications

A circulating miR-19b-based model in diagnosis of human breast cancer

A circulating miR-19b-based model in diagnosis of human breast cancer

Sustained induction of IP-10 by MRP8/14 via the IFNβ–IRF7 axis in macrophages exaggerates lung injury in endotoxemic mice

The Immunomodulatory Role of Cell-Free Approaches in SARS-CoV-2-Induced Cytokine Storm—A Powerful Therapeutic Tool for COVID-19 Patients

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