What Urinary Exosomes Can Reveal about Human Health?

What are exosomes?
Role of exosomes
What role do urinary exosomes play in disease research?
Urinary exosomes as prostate cancer response markers
Early lupus nephritis detection by exosomes
Limitations and future prospects
References 
Further reading


Exosomes have become a major focus in modern biomedical research as scientists attempt to understand the underlying causes of illness, identify novel biomarkers, and develop effective therapeutics.

Urinary exosomes have been shown to play an important role in human disease pathophysiology and can be used as therapeutic targets, which is discussed in this article.

​​​​​​​Image Credit: JasonDrees/Shutterstock.com​​​​​​​Image Credit: JasonDrees/Shutterstock.com

What are exosomes?

Human cells release exosomes from plasma membrane–multivesicular body fusions. Exosomes are involved in metabolic activities, cell waste disposal, protein and nucleic acid exchange, coagulation, and immunological function. Cells release 50–150 nm diameter exosomes granular in structure.

Their surface comprises lipids and proteins from cell membranes, while their inner contains nucleic acids such as microRNA, messenger RNA, DNA, and proteins. Exosomes are known to be extracellular vesicles, including micro-vesicles, apoptotic bodies, and exosomes.

Exosomes are endosomal organelles taken in by cells by endocytosis, fused with the plasma membrane, and secreted into the extracellular space. Exosomes' exterior comprises cell membrane components and their inside contains intracellular chemicals, reflecting the original cells that released them.

The Science of Exosomes

Role of exosomes

Exosomes play an important role in maintaining homeostasis by regulating a broad range of metabolic activities in the human body. Exosomes also provide evidence of interorgan communication. They can also be used as molecular vehicles for medication delivery.

Exosomes play a critical role in cell communication by transporting messages between them. Exosomes can effectively transfer functioning cell nucleic acids (microRNA, messenger RNA) from donor to destination cells.

The contents of exosomes that have been taken up are assumed to have a functional influence in the recipient cell because secreted exosomes act on receptors on the surface of the recipient cells to initiate signal transduction.

What role do urinary exosomes play in disease research?

The researchers are trying to understand the relation between urinary exosomes and kidney function and disorders. Exosomes carry cargo across kidney cells, modify proteome and recipient cell function and represent nephron intercellular signaling.

Urinary exosomes are noteworthy due of their availability, simplicity of sample collection, and non-invasive nature. Non-invasive exosomes provide a cost-effective way to explore disease causes and therapeutic targets due to their diagnostic and prognostic sensitivity.

Non-invasive biomarkers have more clinical and patient adoption than invasive ones. Cost-effective and conveniently distributable urinary indicators are clinically accessible.

They may be used to diagnose at-risk populations and individuals with clinically significant symptoms. Urine proteins and peptides can be used to study proximal, distant, and systemic disorders.

Exosomes are implicated in cardiovascular and renal physiology. Biomarkers may help in mineralocorticoid hypertension. Exosomes deliver RNA and proteins that affect kidney biology.

Exosomes may assist detect arterial hypertension subtypes, enable more suitable therapies, and enhance patient quality of life. Exosomes in hypertension require further study.

Urinary exosomes as prostate cancer response markers

Prostate cancer development, metastasis, and treatment resistance are linked to exosomes including miRNAs, lncRNAs, and proteins. Prostate cancer cells influence stromal cells through exosomes. Affected stromal cells use exosomes to promote tumor development and metastasis.

Exosomes from prostate cancer cells boost chemosensitivity. The exosomes' lipid bilayer membrane makes them ideal transporters of prostate cancer medicines. In addition, exosomes may be extracted from bodily fluids to diagnose prostate cancer.

A prostate cancer diagnosis using exosomes

Prostate specific antigen (PSA) and carbohydrate antigens exhibit false-negatives, false-positives, and lack of tumor-type specificity. Tumor biopsy is conclusive but invasive; hence, clinicians need new prostate cancer biomarkers.

The researchers in an article published the journal of European Urology which states that the exosomes named as microRNAs miR-1290 and miR-375 in CRPC patients' plasma show promise as predictive biomarkers.

Their research findings provide compelling early evidence in favor of the idea that alterations in exosome RNA contents are strong possibilities as clinical diagnostics for advanced prostate cancer (PCa) and that circulating exosomal RNAs comprise a wide variety of RNA types.

Utilizing urinary exosomes for proximity disease study

Urinary exosomes are important in disease development and as therapeutic targets. Urinary exosomes can diagnose renal-related proximity illnesses. MiR-21, miR-29c, and miR-150 are exosomal miRNAs that may predict disease progression in lupus nephritis (LN).

Exosomes from urine have been linked to the pathogenesis of genitourinary disorders. Researchers published an article in the journal of Biomedical Chemistry in which they found that urine micro-vesicles and proteins in prostate cancer patients engage in disease signaling.

Using miRCURY LNA miRNA qPCR Panels, researchers compared 84 miRNAs from healthy males, patients with benign prostate hyperplasia, and prostate cancer patients. All patient groups had miRNA subgroups with varied urine fraction distributions. Two families of miRNAs are implicated in prostate cancer signaling pathways.

Early lupus nephritis detection by exosomes

Two-thirds of lupus patients develop Lupus Nephritis. Despite breakthroughs in treatment, 10–30% of people develop end-stage renal disease (ESRD). Inflammation and fibrosis are frequent in CKD that progresses to ESRD.

Renal biopsy is the "gold standard" for assessing kidney disease, although its invasive nature prevents recurrent testing. Thus, disease progression and therapeutic monitoring are inadequate.

An article published in Nephrol Dial Transplant states that the exosomes in the urine are micro-vesicles that every epithelial cell secretes. facing the urinary tract, provide an excellent marker source for kidney damage and dysfunction.

Researchers discovered that miR-29c linked with renal chronicity but not with renal function, indicating that it might be employed as a potential non-invasive predictor of early progression to fibrosis in patients with LN.

Limitations and future prospects

Although urine exosomal markers may have vast uses in local, distant, or systemic disorders, it is crucial to identify and overcome confounder effects.

These confounders may occur during sample collection, transit, storage, and dilution. Other complicating variables include specific gravity, osmolality, urine creatinine, and conductivity. Thus, normalizing strategies should be studied.

Most urine exosome-based indicators are not used in clinical practice due to performance differences, limited reliability, and expensive prices. Other issues include lack of consistency and time-consuming isolation processes.

In the future, high-throughput techniques that account for biases and provide the needed sensitivity, reproducibility, and specificity will be able to meet the unmet demands of clinical diagnostic processes.

References

  • Huang, X. et al. (2014) ‘Exosomal miR-1290 and miR-375 as Prognostic Markers in Castration-resistant Prostate Cancer’, Bone, 23(1), pp. 1–7. doi.org/10.1016/j.eururo.2014.07.035.Exosomal.
  • Mitchell, P.J. et al. (2009) ‘Can urinary exosomes act as treatment response markers in prostate cancer?’, Journal of Translational Medicine, 7(of 8), pp. 1–13. doi.org/10.1186/1479-5876-7-4.
  • Pan, J. et al. (2017) ‘Exosomes in diagnosis and therapy of prostate cancer’, Oncotarget, 8(57), pp. 97693–97700. doi.org/10.18632/oncotarget.18532.
  • Sole, C. et al. (2015) ‘MIR-29c in urinary exosomes as predictor of early renal fibrosis in lupus nephritis’, Nephrology Dialysis Transplantation, 30(9), pp. 1488–1496. doi.org/10.1093/ndt/gfv128.
  • Vitorino, R. et al. (2021) ‘What can urinary exosomes tell us?’, Cellular and Molecular Life Sciences, 78(7), pp. 3265–3283. doi.org/10.1007/s00018-020-03739-w.
  • Zaporozhchenko, I.A. et al. (2018) ‘Representation Analysis of miRNA in Urine Microvesicles and Cell-Free Urine in Prostate Diseases’, Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry, 12(2), pp. 156–163. doi.org/10.1134/S1990750818020142.

Further Research 

Last Updated: Sep 14, 2023

Maira Ahsan

Written by

Maira Ahsan

During the coronavirus disease 2019 (Covid-19) lockdown, while pursuing a bachelor's degree in human nutrition and dietetics, Maira started her freelancing career as a content writer, focusing on the life sciences. In 2020, she started working as a freelancer on Fiverr, where she quickly found opportunities to work with several Canadian companies. Maira received an offer for a nutritionist position from a French hotel in Canada, where she was responsible for developing nutrition-based recipes and calorie-counted meals.

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