Candidate Biomarkers in Exosome-like Vesicles Purified from Rat and Mouse Urine Samples

Overview

Journal Proteomics Clin Appl

Specialty Biochemistry

Date 2010 Jun 11

PMID 20535238

Citations 66

Authors

Javier Conde-Vancells

Eva Rodriguez-Suarez

Esperanza Gonzalez

Agustin Berisa

David Gil

Nieves Embade

Mikel Valle

Zigmund Luka

Felix Elortza

Conrad Wagner

Shelly C Lu

Jose M Mato

M Falcon-Perez

Affiliations

Soon will be listed here.

Abstract

Purpose: There is a compelling clinical imperative to identify discerning molecular biomarkers of hepatic disease in order to inform the diagnosis, prognosis and treatment.

Experimental Design: We have investigated the proteome of urinary vesicles present in urine samples obtained from experimental models for the study of liver injury, as an approach for identifying potential biomarkers for hepatic disease.

Results: The biochemical and proteomic characterization of highly purified exosome-like urinary vesicles has identified 28 proteins previously unreported in these vesicles, and many that have been previously associated with diseases, such as the prion-related protein. Furthermore, in urine samples from D-galactosamine-treated rats, a well-characterized experimental model for acute liver injury, we have detected a severe reduction in some proteins that normally are clearly detected in urinary vesicles. Finally, differential protein content on urinary vesicles from a mouse model for chronic liver injury has been also identified.

Conclusions And Clinical Relevance: Our results argue positively that urinary vesicles could be a source for identifying non-invasive biomarkers of liver injury. We proposed some proteins such as Cd26, Cd81, Slc3A1 and Cd10 that have been found to be differentially expressed in urinary vesicles from some of the analyzed models as potential biomarkers for liver injury.

Citing Articles

The Role of Extracellular Vesicles in the Development and Treatment of Psoriasis: Narrative Review.

Tang B, Bi Y, Zheng X, Yang Y, Huang X, Yang K Pharmaceutics. 2025; 16(12.

PMID: 39771564 PMC: 11677080. DOI: 10.3390/pharmaceutics16121586.

Exosome-based therapies for inflammatory disorders: a review of recent advances.

Saleem M, Shahzad K, Marryum M, Singh S, Zhou Q, Du S Stem Cell Res Ther. 2024; 15(1):477.

PMID: 39695750 PMC: 11657721. DOI: 10.1186/s13287-024-04107-2.

Extracellular vesicles released by steatotic hepatocytes alter adipocyte metabolism.

Mleczko J, Royo F, Samuelson I, Clos-Garcia M, Williams C, Cabrera D J Extracell Biol. 2024; 1(2):e32.

PMID: 38938664 PMC: 11080919. DOI: 10.1002/jex2.32.

Therapeutic potential of exosomes derived from mesenchymal stem cells for treatment of systemic lupus erythematosus.

Samavati S, Yarani R, Kiani S, Hoseinkhani Z, Mehrabi M, Levitte S J Inflamm (Lond). 2024; 21(1):20.

PMID: 38867277 PMC: 11170788. DOI: 10.1186/s12950-024-00381-2.

Role of extracellular vesicles in nonalcoholic fatty liver disease.

Jiang W, Xu Y, Chen J, Lee Y, Hu Y, Liu C Front Endocrinol (Lausanne). 2023; 14:1196831.

PMID: 37534206 PMC: 10392952. DOI: 10.3389/fendo.2023.1196831.

References

Xiao S, Wang H, Hart J, Fleming D, Beard M . cDNA arrays and immunohistochemistry identification of CD10/CALLA expression in hepatocellular carcinoma. Am J Pathol. 2001; 159(4):1415-21. PMC: 1850507. DOI: 10.1016/S0002-9440(10)62528-X. View

Cohen A, Bunn P, Franklin W, Magill-Solc C, Hartmann C, Helfrich B . Neutral endopeptidase: variable expression in human lung, inactivation in lung cancer, and modulation of peptide-induced calcium flux. Cancer Res. 1996; 56(4):831-9. View

Conde-Vancells J, Rodriguez-Suarez E, Embade N, Gil D, Matthiesen R, Valle M . Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. J Proteome Res. 2009; 7(12):5157-66. PMC: 2696236. DOI: 10.1021/pr8004887. View

Keppler D, Lesch R, REUTTER W, Decker K . Experimental hepatitis induced by D-galactosamine. Exp Mol Pathol. 1968; 9(2):279-90. DOI: 10.1016/0014-4800(68)90042-7. View

Andrieu T, Thibault V, Malet I, Laporte J, Bauvois B, Agut H . Similar increased serum dipeptidyl peptidase IV activity in chronic hepatitis C and other viral infections. J Clin Virol. 2003; 27(1):59-68. DOI: 10.1016/s1386-6532(02)00128-2. View

Firneisz G, Lakatos P, Szalay F . Serum dipeptidyl peptidase IV (DPP IV, CD26) activity in chronic hepatitis C. Scand J Gastroenterol. 2001; 36(8):877-80. DOI: 10.1080/003655201750313423. View

Thery C, Amigorena S, Raposo G, Clayton A . Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol. 2008; Chapter 3:Unit 3.22. DOI: 10.1002/0471143030.cb0322s30. View

Lu S, Mato J . S-Adenosylmethionine in cell growth, apoptosis and liver cancer. J Gastroenterol Hepatol. 2008; 23 Suppl 1:S73-7. PMC: 2408691. DOI: 10.1111/j.1440-1746.2007.05289.x. View

Eggstein S, Kreisel W, Gerok W, EGGSTEIN M . [Dipeptidyl aminopeptidase IV in hospitalized patients and in galactosamine hepatitis of the rat: Activity and lectin affinity chromatography in serum and hepatic plasma membranes]. J Clin Chem Clin Biochem. 1989; 27(9):547-54. View

10.

Zhou H, Pisitkun T, Aponte A, Yuen P, Hoffert J, Yasuda H . Exosomal Fetuin-A identified by proteomics: a novel urinary biomarker for detecting acute kidney injury. Kidney Int. 2006; 70(10):1847-57. PMC: 2277342. DOI: 10.1038/sj.ki.5001874. View

11.

Borscheri N, Roessner A, Rocken C . Canalicular immunostaining of neprilysin (CD10) as a diagnostic marker for hepatocellular carcinomas. Am J Surg Pathol. 2001; 25(10):1297-303. DOI: 10.1097/00000478-200110000-00011. View

12.

El-Mofty S, Scrutton M, Serroni A, Nicolini C, Farber J . Early, reversible plasma membrane injury in galactosamine-induced liver cell death. Am J Pathol. 1975; 79(3):579-96. PMC: 1912733. View

13.

Vella L, Sharples R, Lawson V, Masters C, Cappai R, Hill A . Packaging of prions into exosomes is associated with a novel pathway of PrP processing. J Pathol. 2007; 211(5):582-590. DOI: 10.1002/path.2145. View

14.

Pekonen F, Nyman T, Ammala M, Rutanen E . Decreased expression of messenger RNAs encoding endothelin receptors and neutral endopeptidase 24.11 in endometrial cancer. Br J Cancer. 1995; 71(1):59-63. PMC: 2033444. DOI: 10.1038/bjc.1995.12. View

15.

Koiso K, Akaza H, Ohtani M, Miyanaga N, Aoyagi K . A new tumor marker for bladder cancer. Int J Urol. 1994; 1(1):33-6. DOI: 10.1111/j.1442-2042.1994.tb00005.x. View

16.

Fevrier B, Vilette D, Archer F, Loew D, Faigle W, Vidal M . Cells release prions in association with exosomes. Proc Natl Acad Sci U S A. 2004; 101(26):9683-8. PMC: 470735. DOI: 10.1073/pnas.0308413101. View

17.

Papandreou C, Usmani B, Geng Y, Bogenrieder T, Freeman R, Wilk S . Neutral endopeptidase 24.11 loss in metastatic human prostate cancer contributes to androgen-independent progression. Nat Med. 1998; 4(1):50-7. DOI: 10.1038/nm0198-050. View

18.

Robertson C, Booth S, Beniac D, Coulthart M, Booth T, McNicol A . Cellular prion protein is released on exosomes from activated platelets. Blood. 2006; 107(10):3907-11. DOI: 10.1182/blood-2005-02-0802. View

19.

Gohring B, Holzhausen H, Meye A, Heynemann H, Rebmann U, Langner J . Endopeptidase 24.11/CD10 is down-regulated in renal cell cancer. Int J Mol Med. 1998; 2(4):409-14. DOI: 10.3892/ijmm.2.4.409. View

20.

Mitchell P, Welton J, Staffurth J, Court J, Mason M, Tabi Z . Can urinary exosomes act as treatment response markers in prostate cancer?. J Transl Med. 2009; 7:4. PMC: 2631476. DOI: 10.1186/1479-5876-7-4. View