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Extracellular vesicles from endometriosis patients are characterized by a unique miRNA-lncRNA signature
Kasra Khalaj, … , Madhuri Koti, Chandrakant Tayade
Kasra Khalaj, … , Madhuri Koti, Chandrakant Tayade
Published September 19, 2019
Citation Information: JCI Insight. 2019;4(18):e128846. https://doi.org/10.1172/jci.insight.128846.
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Research Article Reproductive biology

Extracellular vesicles from endometriosis patients are characterized by a unique miRNA-lncRNA signature

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Abstract

With multifactorial etiologies, combined with disease heterogeneity and a lack of suitable diagnostic markers and therapy, endometriosis remains a major reproductive health challenge. Extracellular vesicles (EVs) have emerged as major contributors of disease progression in several conditions, including a variety of cancers; however, their role in endometriosis pathophysiology has remained elusive. Using next-generation sequencing of EVs obtained from endometriosis patient tissues and plasma samples compared with controls, we have documented that patient EVs carry unique signatures of miRNAs and long noncoding RNAs (lncRNAs) reflecting their contribution to disease pathophysiology. Mass spectrophotometry–based proteomic analysis of EVs from patient plasma and peritoneal fluid further revealed enrichment of specific pathways, as well as altered immune and metabolic processes. Functional studies in endometriotic epithelial and endothelial cell lines using EVs from patient plasma and controls clearly indicate autocrine uptake and paracrine cell proliferative roles, suggestive of their involvement in endometriosis. Multiplex cytokine analysis of cell supernatants in response to patient and control plasma–derived EVs indicate robust signatures of important inflammatory and angiogenic cytokines known to be involved in disease progression. Collectively, these findings suggest that endometriosis-associated EVs carry unique cargo and contribute to disease pathophysiology by influencing inflammation, angiogenesis, and proliferation within the endometriotic lesion microenvironment.

Authors

Kasra Khalaj, Jessica E. Miller, Harshavardhan Lingegowda, Asgerally T. Fazleabas, Steven L. Young, Bruce A. Lessey, Madhuri Koti, Chandrakant Tayade

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Figure 1

Characterization of Extracellular vesicles, including exosomes, in endometriosis patient samples, HUVEC, and endometrial and endometriotic epithelial cells.

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Characterization of Extracellular vesicles, including exosomes, in endom...
Transmission electron microscopy scans of purified extracellular vesicles (EVs), including exosomes, derived from endometriosis patient plasma, control plasma, and peritoneal fluid. (A). Extracellular vesicles, including exosomes, ranging in size from approximately 30–120 nm were detected in all 3 groups of patient samples (arrows point to isolated EVs in each group), and all group EVs displayed a cup-shaped morphology — a key signature of intact EV morphology. (B) Exosomal marker probing using Western blotting illustrated positivity of tetraspanin exosomal marker CD63 in all EV groups, as well as in cell lysate from 12Z cultured cells. The endoplasmic reticulum marker CANX was negative for all EV groups and positive for the cell lysate.

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