Exosomal miRNA Profiling to Identify Nanoparticle Phagocytic Mechanisms

MicroRNAs (miRNAs) are short, non-coding RNA species that are important post-transcriptional regulators of gene expression and play an important role in the pathogenesis of non-alcoholic fatty liver disease. Here, we investigated the phosphodiesterase 5 (PDE5) inhibitor induced effects on hepatic and plasma exosomal miRNA expression in CCl4-treated rats. In the present study, hepatic miRNA profiling was conducted using the Nanostring nCounter technology and mRNA profiling using RNA sequencing from PDE5 treated rats in the model of CCl4-induced liver fibrosis. To evaluate if the PDE5 inhibitor affected differentially expressed miRNAs in the liver can be detected in plasma exosomes, qRT-PCR specific assays were used. In livers from CCl4-treated rats, the expression of 22 miRNAs was significantly increased (>1.5-fold, adj. p < 0.05), whereas the expression of 16 miRNAs was significantly decreased (>1.5-fold, adj. p < 0.05). The majority of the deregulated miRNA species are implicated in fibrotic and inflammatory processes. The PDE5 inhibitor suppressed the induction of pro-fibrotic miRNAs, such as miR-99b miR-100 and miR-199a-5p, and restored levels of anti-fibrotic miR-122 and miR-192 in the liver. In plasma exosomes, we observed elevated levels of miR-99b, miR-100 and miR-142-3p after treatment with the PDE5-inhibitor compared to CCl4/Vehicle-treated. Our study demonstrated for the first time that during the development of hepatic fibrosis in the preclinical model of CCl4-induced liver fibrosis, defined aspects of miRNA regulated liver pathogenesis are influenced by PDE5 treatment. In conclusion, miRNA profiling of plasma exosomes might be used as a biomarker for NASH progression and monitoring of treatment effects.

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Exosomal miRNA Profiling to Identify Nanoparticle Phagocytic Mechanisms

Small ◽

10.1002/smll.201704008 ◽

2018 ◽

Vol 14 (15) ◽

pp. 1704008 ◽

Cited By ~ 9

Author(s):

Lin Zhang ◽

Changfu Hao ◽

Sanqiao Yao ◽

Rong Tang ◽

Wei Guo ◽

...

Keyword(s):

Mirna Profiling ◽

Exosomal Mirna

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Circulating Exosomal miRNA Signature in Gestational Diabetes Mellitus Influences Glucose Metabolism in Placental Cells

Diabetes ◽

10.2337/db18-164-lb ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 164-LB

Author(s):

SOUMYALEKSHMI NAIR ◽

VALESKA ORMAZABAL ◽

NANTHINI JAYABALAN ◽

DOMINIC GUANZON ◽

ANDREW LAI ◽

...

Keyword(s):

Diabetes Mellitus ◽

Glucose Metabolism ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Mirna Signature ◽

Placental Cells ◽

Exosomal Mirna

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miRNA profiling in autism spectrum disorder in China

Genomics Data ◽

10.1016/j.gdata.2015.08.006 ◽

2015 ◽

Vol 6 ◽

pp. 108-109 ◽

Cited By ~ 3

Author(s):

Fengzhen Huang ◽

Tieqiao Zhou ◽

Xiaoxi Yao ◽

Jiping Yi ◽

Fei Zhou ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Mirna Profiling

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Regulation of Serum Exosomal MicroRNAs in Mice Infected with Orientia tsutsugamushi

Microorganisms ◽

10.3390/microorganisms9010080 ◽

2020 ◽

Vol 9 (1) ◽

pp. 80

Author(s):

Le Jiang ◽

Tatyana Belinskaya ◽

Zhiwen Zhang ◽

Teik-Chye Chan ◽

Wei-Mei Ching ◽

...

Keyword(s):

Post Infection ◽

Viral Infections ◽

Scrub Typhus ◽

Late Phase ◽

Many Body ◽

Host Immune Responses ◽

Lethal Infection ◽

Exosomal Mirnas ◽

Exosomal Mirna ◽

Intercellular Communications

Exosomes are small extracellular vesicles that carry proteins, lipids, and nucleic acids. They are circulated in many body fluids and play an important role in intercellular communications. MicroRNAs (miRNAs), as major components of exosomes, are often regulated in many diseases including bacterial and viral infections. Functionally, exosome-carried miRNAs interact with various immune cells and affect their behavior. Little is known whether exosomal miRNAs are regulated during scrub typhus, a potentially lethal infection caused by intracellular bacteria, Orientiatsutsugamushi. In the present study, we utilized a scrub typhus mouse model and collected serum at various time points post infection. A custom quantitative PCR array covering 92 murine miRNAs was used to profile serum exosomal miRNAs. A total of 12 miRNAs were found to be significantly up- or down-regulated at least at one time point post infection when compared to uninfected animals. Further analysis identified multiple miRNAs in the let-7 family that were consistently down-regulated at early and late phase of infection. Functionally, serum exosomes isolated from infected mice displayed strong proinflammatory effect when incubated with bone marrow-derived macrophages. Our data revealed dynamic regulations of serum exosomal miRNA during scrub typhus infection, which could significantly influence host immune responses and disease outcome.

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Plasma Exosomal miRNA Levels after Radiotherapy Are Associated with Early Progression and Metastasis of Cervical Cancer: A Pilot Study

Journal of Clinical Medicine ◽

10.3390/jcm10102110 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2110

Author(s):

Oyeon Cho ◽

Do-Wan Kim ◽

Jae-Youn Cheong

Keyword(s):

Cervical Cancer ◽

Pilot Study ◽

Biological Functions ◽

Patients With Cancer ◽

Initial Stage ◽

Exosomal Mirnas ◽

Early Progression ◽

Before And After ◽

Microenvironmental Factors ◽

Exosomal Mirna

Plasma exosomal miRNAs are key regulators of cell-cell interactions associated with several biological functions in patients with cancer. This pilot study aimed to investigate the log2 fold change (log2FC) of the expression of exosomal miRNAs and related mRNAs in the blood of patients with cervical cancer to identify prognostic markers better than those currently available. We sequenced plasma exosomal RNA from 56 blood samples collected from 28 patients with cervical cancer, who had been treated with concurrent chemoradiotherapy (CCRT). Changes in the expression of miRNAs and mRNAs before and after CCRT were represented as log2FC. Their biological functions were studied by miRNA-mRNA network analysis, using ingenuity pathway analysis, after the selection of two groups of miRNAs, each associated with early progression (EP) and metastasis, also described as initial stage. Seven patients experienced EP, three of whom died within four months after progression. Reduced levels of miR-1228-5p, miR-33a-5p, miR-3200-3p, and miR-6815-5p and increased levels of miR-146a-3p in patients with EP revealed unresolved inflammation, with accompanying increased expression of PCK1 and decreased expression of FCGR1A. Increased levels of miR-605-5p, miR-6791-5p, miR-6780a-5p, and miR-6826-5p and decreased levels of miR-16-1-3p (or 15a-3p) were associated with the degree of metastasis and led to the systemic activation of myeloid, endothelial, and epithelial cells, as well as neurons, phagocytes, and platelets. Log2FCs in the expression of miRNAs and mRNAs from plasma exosomes after CCRT are associated with EP and metastasis, reflecting unresolved inflammation and systemic microenvironmental factors, respectively. However, this study, supported by preliminary data insufficient to reach clear conclusions, should be verified in larger prospective cohorts.

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Exosomes derived from miR-126-3p-overexpressing synovial fibroblasts suppress chondrocyte inflammation and cartilage degradation in a rat model of osteoarthritis

Cell Death Discovery ◽

10.1038/s41420-021-00418-y ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yan Zhou ◽

Jianghua Ming ◽

Yaming Li ◽

Bochun Li ◽

Ming Deng ◽

...

Keyword(s):

Synovial Fluid ◽

Apoptotic Cell ◽

Synovial Fibroblasts ◽

Cartilage Degeneration ◽

Cartilage Degradation ◽

Exosomal Mirnas ◽

Exosomal Mirna ◽

And Control ◽

And Cartilage

AbstractMicroRNAs (miRNAs) encapsulated within exosomes can serve as essential regulators of intercellular communication and represent promising biomarkers of several aging-associated disorders. However, the relationship between exosomal miRNAs and osteoarthritis (OA)-related chondrocytes and synovial fibroblasts (SFCs) remain to be clarified. Herein, we profiled synovial fluid-derived exosomal miRNAs and explored the effects of exosomal miRNAs derived from SFCs on chondrocyte inflammation, proliferation, and survival, and further assessed their impact on cartilage degeneration in a surgically-induced rat OA model. We identified 19 miRNAs within synovial fluid-derived exosomes that were differentially expressed when comparing OA and control patients. We then employed a microarray-based approach to confirm that exosomal miRNA-126-3p expression was significantly reduced in OA patient-derived synovial fluid exosomes. At a functional level, miRNA-126-3p mimic treatment was sufficient to promote rat chondrocyte migration and proliferation while also suppressing apoptosis and IL-1β, IL-6, and TNF-α expression. SFC-miRNA-126-3p-Exos were able to suppress apoptotic cell death and associated inflammation in chondrocytes. Our in vivo results revealed that rat SFC-derived exosomal miRNA-126-3p was sufficient to suppress the formation of osteophytes, prevent cartilage degeneration, and exert anti-apoptotic and anti-inflammatory effects on articular cartilage. Overall, our findings indicate that SFC exosome‐delivered miRNA-126-3p can constrain chondrocyte inflammation and cartilage degeneration. As such, SFC-miRNA-126-3p-Exos may be of therapeutic value for the treatment of patients suffering from OA.

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