Characterization of extracellular vesicle miRNA identified in peripheral blood of chronic pancreatitis patients

Desai, Chirag S.; Khan, Aisha; Bellio, Michael; Willis, Micah L; Mahung, Cressida; Ma, Xiaobo; Baldwin, Xavier; Williams, Brittney M.; Baron, Todd H.; Coleman, Leon G.; Wallet, Shannon M.; Maile, Robert

doi:10.1007/s11010-021-04248-5

Cited by 9 publications

(13 citation statements)

References 38 publications

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“…In addition to serum and plasma samples, one recent study investigated miRs levels in plasma-derived EV from 15 CP patients [ 174 ]. The expression levels of miR-579-3p were significantly reduced in CP patients compared to healthy controls [ 174 ]. Other EV-based studies were based on a relatively large number of EV samples from 90 patients with PDAC or CP [ 174 ].…”

Section: Biomarkers and Therapeutic Approachesmentioning

confidence: 99%

The Role of MicroRNAs in Pancreatitis Development and Progression

Patel

Almanzar

LaComb

et al. 2023

IJMS

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Pancreatitis (acute and chronic) is an inflammatory disease associated with significant morbidity, including a high rate of hospitalization and mortality. MicroRNAs (miRs) are essential post-transcriptional modulators of gene expression. They are crucial in many diseases’ development and progression. Recent studies have demonstrated aberrant miRs expression patterns in pancreatic tissues obtained from patients experiencing acute and chronic pancreatitis compared to tissues from unaffected individuals. Increasing evidence showed that miRs regulate multiple aspects of pancreatic acinar biology, such as autophagy, mitophagy, and migration, impact local and systemic inflammation and, thus, are involved in the disease development and progression. Notably, multiple miRs act on pancreatic acinar cells and regulate the transduction of signals between pancreatic acinar cells, pancreatic stellate cells, and immune cells, and provide a complex interaction network between these cells. Importantly, recent studies from various animal models and patients’ data combined with advanced detection techniques support their importance in diagnosing and treating pancreatitis. In this review, we plan to provide an up-to-date summary of the role of miRs in the development and progression of pancreatitis.

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Section: Biomarkers and Therapeutic Approachesmentioning

confidence: 99%

The Role of MicroRNAs in Pancreatitis Development and Progression

Patel

Almanzar

LaComb

et al. 2023

IJMS

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show abstract

“…Media samples were diluted in 0.02 µm filtered PBS and assessed by NTA on the ParticleMetrix ZetaView ® PMX-420 Video Microscope in the Nanomedicines Characterization Core Facility at UNC as we have reported previously (31,(49)(50)(51).…”

Section: Nanoparticle Tracking Analysis (Nta)mentioning

confidence: 99%

Ethanol Induces Secretion of Proinflammatory Extracellular Vesicles That Inhibit Adult Hippocampal Neurogenesis Through G9a/GLP-Epigenetic Signaling

et al. 2022

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Adult hippocampal neurogenesis (AHN) is involved in learning and memory as well as regulation of mood. Binge ethanol reduces AHN, though the mechanism is unknown. Microglia in the neurogenic niche are important regulators of AHN, and ethanol promotes proinflammatory microglia activation. We recently reported that extracellular vesicles (EVs) mediate ethanol-induced inflammatory signaling in microglia. Therefore, we investigated the role of EVs in ethanol-induced loss of adult hippocampal neurogenesis. At rest, microglia promoted neurogenesis through the secretion of pro-neurogenic extracellular vesicles (pn-EVs). Depletion of microglia using colony-stimulating factor 1 receptor (CSFR1) inhibition in vivo or using ex vivo organotypic brain slice cultures (OBSCs) caused a 30% and 56% loss of neurogenesis in the dentate, respectively, as measured by immunohistochemistry for doublecortin (DCX). Likewise, chemogenetic inhibition of microglia using a CD68.hM4di construct caused a 77% loss in OBSC, indicating a pro-neurogenic resting microglial phenotype. EVs from control OBSC were pro-neurogenic (pn-EVs), enhancing neurogenesis when transferred to other naive OBSC and restoring neurogenesis in microglia-depleted cultures. Ethanol inhibited neurogenesis and caused secretion of proinflammatory EVs (EtOH-EVs). EtOH-EVs reduced hippocampal neurogenesis in naïve OBSC by levels similar to ethanol. Neurogenesis involves complex regulation of chromatin structure that could involve EV signaling. Accordingly, EtOH-EVs were found to be enriched with mRNA for the euchromatin histone lysine methyltransferase (Ehm2t/G9a), an enzyme that reduces chromatin accessibility through histone-3 lysine-9 di-methylation (H3K9me2). EtOH-EVs induced G9a and H3K9me2 by 2-fold relative to pn-EVs in naïve OBSCs. Pharmacological inhibition of G9a with either BIX-01294 or UNC0642 prevented loss of neurogenesis caused by both EtOH and EtOH-EVs. Thus, this work finds that proinflammatory EtOH-EVs promote the loss of adult hippocampal neurogenesis through G9a-mediated epigenetic modification of chromatin structure.

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“…Therefore, exosomes have been established as ideal biomarkers and have been widely used in disease diagnosis, prognosis evaluation, and treatment monitoring. The diagnostic and prognostic value of exosomes in pancreatic diseases such as pancreatic cancer and chronic pancreatitis has been widely confirmed [ 190 , 191 , 192 , 193 ].…”

Section: Exosome-based Diagnostic Strategymentioning

confidence: 99%

Fighting Fire with Fire: Exosomes and Acute Pancreatitis-Associated Acute Lung Injury

et al. 2022

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Acute pancreatitis (AP) is a prevalent clinical condition of the digestive system, with a growing frequency each year. Approximately 20% of patients suffer from severe acute pancreatitis (SAP) with local consequences and multi-organ failure, putting a significant strain on patients’ health insurance. According to reports, the lungs are particularly susceptible to SAP. Acute respiratory distress syndrome, a severe type of acute lung injury (ALI), is the primary cause of mortality among AP patients. Controlling the mortality associated with SAP requires an understanding of the etiology of AP-associated ALI, the discovery of biomarkers for the early detection of ALI, and the identification of potentially effective drug treatments. Exosomes are a class of extracellular vesicles with a diameter of 30–150 nm that are actively released into tissue fluids to mediate biological functions. Exosomes are laden with bioactive cargo, such as lipids, proteins, DNA, and RNA. During the initial stages of AP, acinar cell-derived exosomes suppress forkhead box protein O1 expression, resulting in M1 macrophage polarization. Similarly, macrophage-derived exosomes activate inflammatory pathways within endothelium or epithelial cells, promoting an inflammatory cascade response. On the other hand, a part of exosome cargo performs tissue repair and anti-inflammatory actions and inhibits the cytokine storm during AP. Other reviews have detailed the function of exosomes in the development of AP, chronic pancreatitis, and autoimmune pancreatitis. The discoveries involving exosomes at the intersection of AP and acute lung injury (ALI) are reviewed here. Furthermore, we discuss the therapeutic potential of exosomes in AP and associated ALI. With the continuous improvement of technological tools, the research on exosomes has gradually shifted from basic to clinical applications. Several exosome-specific non-coding RNAs and proteins can be used as novel molecular markers to assist in the diagnosis and prognosis of AP and associated ALI.

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Characterization of extracellular vesicle miRNA identified in peripheral blood of chronic pancreatitis patients

Cited by 9 publications

References 38 publications

The Role of MicroRNAs in Pancreatitis Development and Progression

The Role of MicroRNAs in Pancreatitis Development and Progression

Ethanol Induces Secretion of Proinflammatory Extracellular Vesicles That Inhibit Adult Hippocampal Neurogenesis Through G9a/GLP-Epigenetic Signaling

Fighting Fire with Fire: Exosomes and Acute Pancreatitis-Associated Acute Lung Injury

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