Kidney Tissue Exosome Research and Application

Kidney tissue exosomes have a place in the study of tissue exosomes. Each kidney consists of more than 4 million nephron units. Each nephron unit includes three parts: glomerulus, renal capsule, and tubules. The sources of kidney tissue exosomes include renal tissue, tubular tissue, and renal tumor tissue, and are involved in diseases such as chronic kidney disease, acute kidney injury, chronic kidney injury, and kidney cancer. Creative Biolabs has successfully launched services for kidney tissue exosome-related research and applications, and with the extensive project experience already accumulated, can isolate high-purity tissue exosomes from kidney tissue parts We have already accumulated extensive project experience in isolating high-purity tissue exosomes from kidney tissue sites and facilitating services such as characterization, content analysis, and application studies. We have summarized the classical research ideas of renal tissue exosomes, including functional mechanism study, targeting key tissue exosome molecules, clinical significance validation, and in vitro functional validation.

Functional Mechanism Investigations

One study has investigated the functional mechanisms by which renal tubule-derived exosomes play a central role in mediating renal fibrosis. An increased level of exosome secretion was found by quantifying the early stages of unilateral ureteral obstruction, ischemia-reperfusion injury, or 5/6 nephrectomy models. This was observed by detecting CD63 expression in different disease models and controlling kidneys in combination with electron microscopy to observe tissue interstitial exosome secretion. It was further determined that the main source of exosomes in these diseased kidneys was proximal tubular epithelial cells by CD63 immunofluorescence staining and double staining with different fractions of tubular cell-specific marker proteins. Finally, in vitro and in vivo experiments were designed to demonstrate the functional mechanism by which renal tubular-derived exosomes mediate fibroblast activation and renal fibrosis through the ligands of transporting Sonic hedgehog.

Fig.1 Mechanism of renal tubular exosome function. (Liu, 2020)

Targeting Tissue Exosome Key Molecules and Validating Clinical Significance

It is also valuable to target key exosomal molecules and explore their major contributing sites and clinical significance in the disease. The researchers identified miR-19b-3p by screening the exosomal contents of diseased versus normal kidney tissue exosomes in an AKI (acute kidney injury) model through global miRNA profiling. To determine the extent to which tubular tissue exosomal miRNAs contribute to whole kidney tissue exosome miRNA expression, exosomes were isolated from the tubular portion of kidney tissue. Quantitative findings revealed more significant upregulation of miR-19b-3p in tubular tissue exosomes in diseased and normal states, with a 59.7-fold difference between experimental and control groups compared to whole kidney tissue exosomes. Thus, in the AKI model, miRNAs were selectively loaded into renal secretory exosomes, especially in Renal Proximal Tubule Epithelial Cells, with induction of M1 macrophage activation and inflammation onset. Finally, the clinical significance of the increase in exosomal miR-19b-3p in urine samples from diabetic nephropathy was also explored in relation to the severity of tubulointerstitial inflammation.

Fig.2 Injured tubular epithelium-derived exosomes containing miR-19b-3p induce inflammation in M1 macrophages. (Lv, 2020)

Histological Analysis and Functional Validation

After speculating the biological functions of tissue exosomes and screening their key functional molecules, setting up in vitro experiments to validate the functions of cell- and tissue-derived exosomes facilitates the identification of reliable disease-related exosome markers. For example, protein profiling of exosomes isolated from renal cell carcinoma and normal kidney tissue screened for high enrichment of Azurocidin 1, a key molecule of the lesion, and correlation of clinical staging and grading with Azurocidin 1 was verified by differential analysis and western blot. After that, it was essential to perform in vitro experiments to verify the function of exosomes carrying the key molecule. The study verified in vitro experiments that cellular exosomes from renal cell carcinoma and tumor tissue exosomes with Azurocidin 1-dependent disruption of vascular endothelial cell morphology, respectively, showing the great potential of AZU1 in exosomes as a marker for early renal cell carcinoma.

Fig.3 Proteome-wide characterization of kidney tissue exudative EVs. (Jingushi, 2018)

Tissue exosomes are the true functioning exosomes in diseased tissues in vivo. As exosomes of various cellular origins are also pooled in the tissue microenvironment, tissue exosomes are authentic and abundant compared to cell lineage-derived exosomes, and exclusive and innovative compared to humoral exosomes. Comprehensive histological analysis and functional exploration of renal tissue-derived exosomes provide exciting strategies for understanding the physiological functions of exosomes in kidney-related diseases. Creative Biolabs provides services for kidney tissue exosome isolation, histological profiling, and functional studies to deeply explore the significant advantages of tissue exosomes in developing markers and interpreting function. Please contact us to learn more.

References

Liu, X.; et al. Tubule-derived exosomes play a central role in fibroblast activation and kidney fibrosis. Kidney Int. 2020, 97(6): 1181-1195.
Lv, L.L.; et al. Exosomal miRNA-19b-3p of tubular epithelial cells promotes M1 macrophage activation in kidney injury. Cell Death Differ. 2020, 27(1): 210-226.
Jingushi, K.; et al. Extracellular vesicles isolated from human renal cell carcinoma tissues disrupt vascular endothelial cell morphology via azurocidin. Int J Cancer. 2018, 142(3): 607-617.