Exosome Secretion — More Than Simple Waste Disposal? Implications for Physiology, Diagnostics and Therapeutics

Nagarajah, Sivappriyan

doi:10.5772/62975

Cited by 22 publications

(13 citation statements)

References 75 publications

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“…The interphotoreceptor space is in constant contact with RPE microvilli, which are optimally positioned for phagocytic activities (Strauss, 2005). Increasing evidence suggests that various neurons shed vesicles as means of communication and to remove unwanted materials under neurodegenerative conditions (Nagarajah, 2016;Fowler, 2019). More recently, RPE cells have been reported to take up extracellular vesicles in an in vitro cell culture model (Nicholson et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

RPE Cells Engulf Microvesicles Secreted by Degenerating Rod Photoreceptors

Ropelewski

Imanishi

2020

eNeuro

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Rhodopsin is mislocalized to the inner segment plasma membrane (IS PM) in various blinding disorders including autosomal-dominant retinitis pigmentosa caused by class I rhodopsin mutations. In these disorders, rhodopsin-laden microvesicles are secreted into the extracellular milieu by afflicted photoreceptor cells. Using a Xenopus laevis model expressing class I mutant rhodopsin or Na 1 /K 1-ATPase (NKA) fused to Dendra2, we fluorescently labeled the microvesicles and found retinal pigment epithelial (RPE) cells are capable of engulfing microvesicles containing rhodopsin. A unique sorting mechanism allows class I mutant rhodopsin, but not NKA, to be packaged into the microvesicles. Under normal physiological conditions, NKA is not shed as Significance Statement Rhodopsin mislocalization is a common cause of photoreceptor degeneration in inherited blinding disorders. In this study, we describe a novel mechanism of removing rhodopsin molecules from inner segment plasma membrane (IS PM). Mislocalized rhodopsin is packaged into microvesicles, which are secreted into the interphotoreceptor space and cleared via engulfment by retinal pigment epithelial (RPE) cells. While IS PM-mislocalized rhodopsin is specifically packaged into microvesicles, Na 1 /K 1-ATPase a-subunit, an IS PM resident protein, was not sorted into vesicles under either pathologic or normal physiological conditions. Interaction between photoreceptor and RPE cells is critical for maintaining visual function, and its alteration can lead to compromised vision. This study provides novel insights into photoreceptor-RPE cell interaction in inherited blinding disorders.

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Section: Introductionmentioning

confidence: 99%

RPE Cells Engulf Microvesicles Secreted by Degenerating Rod Photoreceptors

Ropelewski

Imanishi

2020

eNeuro

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“…However, in recent years, it has been found that these tiny vesicles contain cell-specific proteins, nucleic acids and lipids, which can be transmitted to other cells as signaling molecules to change their functions. 24 Exosomes can play important roles in many physiological and pathological aspects, such as antigen presentation, growth and migration of tumors, repair of tissue damage, and so on. 25 In addition, exosomes secreted by different cells have unused components and functions, which can be used as biomarkers for disease diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Identification of serum exosomal microRNAs in acute spinal cord injured rats

Ding

Chen

Wang

et al. 2019

Exp Biol Med (Maywood)

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It is important to find specific and easily detectable diagnostic markers in acute stage of spinal cord injury for guiding treatment and estimating prognosis. Although, microRNAs are attractive biomarkers, there is still no uniform standard for clinical evaluation of spinal cord injury based on “free circulation” miRNA spectrum. The reason may be that miRNA analysis from biological fluids is influenced by many pre-analysis variables. Exosome miRNAs are widely distributed in body fluids and have many advantages comparing with free miRNAs. The specific miRNAs in the central nervous system can be transported to the peripheral circulation and concentrated in exosomes. Therefore, we hypothesized that there might be some physiological changes associated with spinal cord injury in serum exosomal miRNAs. Using next-generation sequencing, miRNA profiles in serum exosomes of sham and acute spinal cord injury rats were analyzed, and integrative bioinformatics were used to analyze the function and regulation of putative target genes. The results showed that acute spinal cord injury can lead to changes in miRNA expression in the circulating exosomes. The changed miRNAs and their associated pathways may explain the pathology of acute spinal cord injury. More importantly, we determined serum exosomal miR-125b-5p, miR-152-3p, and miR-130a-3p are specific and easily detectable diagnostic markers in acute spinal cord injury. More interestingly, we also found some valuable known and novel miRNAs. Further bioinformatics analysis and functional research will be of great help to make clear their role in the pathological process of spinal cord injury and judging whether they can be used as diagnostic markers. Impact statement This research hypothesized that there might be some physiological changes associated with SCI in serum exosomal miRNAs. Using next-generation sequencing, miRNA profiles in serum exosomes of sham and acute SCI rats were analyzed, and integrative bioinformatics were used to analyze the function and regulation of putative target genes. The results showed that acute SCI can lead to changes in miRNA expression in the circulating exosomes. The changed miRNAs and their associated pathways may explain the pathology of acute SCI. More importantly, we determined serum exosomal miR-125b-5p, miR-152-3p, and miR-130a-3p are specific and easily detectable diagnostic markers in acute SCI.

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“…In the past decade, there was an extraordinary explosion of research in the field of sEVs. Circulating sEVs have gone from being considered as useless cellular metabolic waste disposal to play an important part in mediation of cell-to-cell communication [32,33]. In our study, as early as 7 days after SAVR, there was a marked increase of circulating sEVs before returning to initial values after 3 mo.…”

Section: Discussionmentioning

confidence: 45%

The Course of Circulating Small Extracellular Vesicles in Patients Undergoing Surgical Aortic Valve Replacement

Weber

Liu

Cardone

et al. 2020

BioMed Research International

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In the last years, increasing efforts have been devoted to investigating the role of small extracellular vesicles (sEVs) in cardiovascular diseases. These nano-sized particles (30-150 nm), secreted by different cell types, contain signalling molecules that enable participation in intercellular communication processes. In this study, we examined the course of circulating sEVs in patients undergoing surgical aortic valve replacement (SAVR) and correlated them with echocardiographic and standard blood parameters. Peripheral blood samples were collected from 135 patients undergoing SAVR preoperatively and at three follow-up points. Circulating sEVs were precipitated using Exoquick™ exosome isolation reagent and analyzed by nanoparticle tracking analysis (NTA). Our findings indicate that no more than 7 days after SAVR, there was a marked increase of circulating sEVs before returning to initial values after 3 months. Further, shear stress is not a trigger for the formation and release of circulating sEVs. Moreover, we pointed out a correlation between circulating sEVs and erythrocytes as well as LDH and creatinine levels in peripheral blood. Finally, all patients with a moderate prosthesis-patient mismatch as well as with an impaired left ventricular mass regression had lower levels of circulating sEVs 3 months after SAVR compared to their respective status before surgery. We conclude that in patients with aortic valve stenosis (AVS), sEVs may play an important part in mediating cell-cell communication and SAVR may have a crucial and lasting impact on their circulating levels. Besides, lower levels of sEVs portend to be associated with inferior recovery after major surgical interventions. The additional use of circulating sEVs beyond echocardiographic and laboratory parameters could have a prognostic value to estimate adverse outcomes in patients undergoing SAVR.

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Exosome Secretion — More Than Simple Waste Disposal? Implications for Physiology, Diagnostics and Therapeutics

Cited by 22 publications

References 75 publications

RPE Cells Engulf Microvesicles Secreted by Degenerating Rod Photoreceptors

RPE Cells Engulf Microvesicles Secreted by Degenerating Rod Photoreceptors

Identification of serum exosomal microRNAs in acute spinal cord injured rats

The Course of Circulating Small Extracellular Vesicles in Patients Undergoing Surgical Aortic Valve Replacement

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