Urinary exosomal expression of activator of G protein signaling 3 in polycystic kidney disease

被引：14

作者：

Keri K.C. ^{[1
]}

Regner K.R. ^{[1
]}

Dall A.T. ^{[1
]}

Park F. ^{[2
]}

机构：

[1] Department of Medicine, Division of Nephrology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, 53226, WI

[2] Department of Pharmaceutical Sciences, University of Tennessee, Health Science Center, College of Pharmacy, 881 Madison Ave, Memphis, 38163, TN

来源：

BMC Research Notes | / 11卷 / 1期

基金：

美国国家卫生研究院;

关键词：

Biomarker; Kidney; Polycystic kidney disease; Urine exosomes; Western blot analysis;

D O I：

10.1186/s13104-018-3467-6

中图分类号：

学科分类号：

摘要：

Objective: PKD is a genetic disease that is characterized by abnormally proliferative epithelial cells in the kidney and liver. Urinary exosomes have been previously examined as a source of unique proteins that may be used to diagnose and monitor the progression of PKD. Previous studies by our group have shown that AGS3, which is a receptor-independent regulator G-proteins, was markedly upregulated in RTECs during kidney injury including PKD. In this study, our goal was to determine whether AGS3 could be measured in exosomes using animals and humans with PKD. Results: In our study, urinary exosomes were isolated from PCK rats and the control Sprague-Dawley (SD) rats. AGS3 expression was significantly increased (P < 0.05) in PKD versus SD rats at 16 weeks of age. This increase was detectable in a time-dependent manner from 8 weeks of age and peaked at ~ 16-20 weeks (length of study). Similarly, in exosomes from human urine samples with PKD, AGS3 expression was significantly increased (P < 0.05) compared to healthy human controls where AGS3 was largely undetectable. In conclusion, the detection of AGS3 in urinary exosomes may be a novel biomarker for PKD, and provide new insight into the biology of tubular epithelial cell function during cystic disease progression. © 2018 The Author(s).

引用

共 26 条

[1]

Patel V., Chowdhury R., Igarashi P., Advances in the pathogenesis and treatment of polycystic kidney disease, Curr Opin Nephrol Hypertens, 18, 2, pp. 99-106, (2009)

[2]

Bae K.T., Zhu F., Chapman A.B., Torres V.E., Grantham J.J., Guay-Woodford L.M., Baumgarten D.A., King B.F., Wetzel L.H., Kenney P.J., Et al., Magnetic resonance imaging evaluation of hepatic cysts in early autosomal-dominant polycystic kidney disease: The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease cohort, Clin J Am Soc Nephrol, 1, 1, pp. 64-69, (2006)

[3]

Chapman A.B., Approaches to testing new treatments in autosomal dominant polycystic kidney disease: Insights from the CRISP and HALT-PKD studies, Clin J Am Soc Nephrol, 3, 4, pp. 1197-1204, (2008)

[4]

Gamez-Valero A., Lozano-Ramos S.I., Bancu I., Lauzurica-Valdemoros R., Borras F.E., Urinary extracellular vesicles as source of biomarkers in kidney diseases, Front Immunol, 6, (2015)

[5]

Pisitkun T., Johnstone R., Knepper M.A., Discovery of urinary biomarkers, Mol Cell Proteomics, 5, 10, pp. 1760-1771, (2006)

[6]

Pisitkun T., Shen R.F., Knepper M.A., Identification and proteomic profiling of exosomes in human urine, Proc Natl Acad Sci USA, 101, 36, pp. 13368-13373, (2004)

[7]

Zhou H., Yuen P.S., Pisitkun T., Gonzales P.A., Yasuda H., Dear J.W., Gross P., Knepper M.A., Star R.A., Collection, storage, preservation, and normalization of human urinary exosomes for biomarker discovery, Kidney Int, 69, 8, pp. 1471-1476, (2006)

[8]

Hogan M.C., Manganelli L., Woollard J.R., Masyuk A.I., Masyuk T.V., Tammachote R., Huang B.Q., Leontovich A.A., Beito T.G., Madden B.J., Et al., Characterization of PKD protein-positive exosome-like vesicles, J Am Soc Nephrol, 20, 2, pp. 278-288, (2009)

[9]

Kwon M., Pavlov T.S., Nozu K., Rasmussen S.A., Ilatovskaya D.V., Lerch-Gaggl A., North L.M., Kim H., Qian F., Sweeney W.E., Et al., G-protein signaling modulator 1 deficiency accelerates cystic disease in an orthologous mouse model of autosomal dominant polycystic kidney disease, Proc Natl Acad Sci USA, 109, 52, pp. 21462-21467, (2012)

[10]

Lenarczyk M., Pressly J.D., Arnett J., Regner K.R., Park F., Localization and expression profile of Group i and II activators of G-protein signaling in the kidney, J Mol Histol, 46, 2, pp. 123-136, (2015)

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