title: Characterization of the renal cyst fluid proteome in autosomal dominant polycystic kidney disease (ADPKD) patients.
abstract: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by localized autonomous cellular proliferation, fluid accumulation within the cysts, and intraparenchymal fibrosis of the kidney. Little is known about the cyst fluid's protein composition. We hypothesized that the complex collection of cyst fluid proteins (cyst fluid proteome) plays a major role in cyst formation/maintenance and contains yet unknown diagnostic and mechanistic features that are common to all forms of PKD. We analyzed five kidney cyst fluids from four patients with ADPKD. Tryptic peptides from plasma-protein immunodepleted (ProteoPrep(R)) and undepleted cyst fluid samples were analyzed by LC-MS/MS. Proteins were identified by SEQUEST and validated via the Trans-Proteomic Pipeline; 391 proteins were identified with >90% confidence; 251 of them in undepleted and 362 in immunodepleted samples. Immunodepletion removed >94% of the cyst fluid protein. A surprisingly large and functionally diverse number of proteins common to most cysts were identified. These proteins may be of mechanistic interest and include Ig gamma, kappa, and fragments; complement components; vitronectin; orosomucoid; prostaglandin D2 synthase; vitamin D-binding protein; clusterin; SERPIN family proteins; hemopexin; and fetuin-A. Additionally, these results suggest that further prefractionation and enhanced chromatographic separation of tryptic peptides is likely to expose an even greater number of relevant proteins.
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, IN, USA.
authors.forename: Xianyin
authors.initials: X
authors.lastname: Lai
authors.forename: Robert L
authors.initials: RL
authors.lastname: Bacallao
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Blazer-Yost
authors.forename: David
authors.initials: D
authors.lastname: Hong
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Mason
authors.forename: Frank A
authors.initials: FA
authors.lastname: Witzmann
references.citation: J Clin Pathol. 1991 Oct;44(10):812-6
references.pmid: 1720435
references.citation: Hum Pathol. 2007 Feb;38(2):239-46
references.pmid: 17056094
references.citation: Am J Kidney Dis. 1995 Mar;25(3):471-7
references.pmid: 7872327
references.citation: N Engl J Med. 1995 Jul 6;333(1):18-25
references.pmid: 7776989
references.citation: Am J Physiol Renal Physiol. 2006 Jan;290(1):F20-34
references.pmid: 16339962
references.citation: Am J Kidney Dis. 1996 Dec;28(6):788-803
references.pmid: 8957030
references.citation: Kidney Int. 2006 Nov;70(10):1847-57
references.pmid: 17021608
references.citation: Anal Biochem. 2004 Oct 1;333(1):174-81
references.pmid: 15351294
references.citation: Nephron. 2000 Jan;84(1):6-12
references.pmid: 10644902
references.citation: Am J Physiol. 1994 Mar;266(3 Pt 2):F459-65
references.pmid: 8160795
references.citation: N Engl J Med. 1993 Jul 29;329(5):310-3
references.pmid: 8321258
references.citation: Lancet. 2007 Apr 14;369(9569):1287-1301
references.pmid: 17434405
references.citation: Cell Tissue Res. 2002 Dec;310(3):289-96
references.pmid: 12457227
references.citation: Kidney Int. 2001 Jul;60(1):37-45
references.pmid: 11422734
references.citation: Anal Chem. 2002 Oct 15;74(20):5383-92
references.pmid: 12403597
references.citation: Kidney Int. 2008 Jan;73(1):63-76
references.pmid: 17960140
references.citation: Kidney Int. 2001 Oct;60(4):1240-8
references.pmid: 11576338
references.citation: Proteomics Clin Appl. 2007 Jan 1;1(1):73-88
references.pmid: 20204147
references.citation: Anal Biochem. 1976 May 7;72:248-54
references.pmid: 942051
references.citation: Bioinformatics. 2004 Dec 12;20(18):3710-5
references.pmid: 15297299
references.citation: Biochim Biophys Acta. 1998 Feb 4;1401(2):203-10
references.pmid: 9531976
references.citation: Kidney Int. 2000 Jun;57(6):2360-74
references.pmid: 10844606
references.citation: Electrophoresis. 2005 Jun;26(11):2117-27
references.pmid: 15880626
references.citation: Nat Genet. 2000 May;25(1):25-9
references.pmid: 10802651
references.citation: DNA Cell Biol. 2002 Apr;21(4):297-306
references.pmid: 12042069
references.citation: Kidney Int. 2002 Nov;62(5):1560-9
references.pmid: 12371956
references.citation: Anat Embryol (Berl). 1998 Feb;197(2):125-33
references.pmid: 9497155
references.citation: Nat Genet. 1995 Jun;10(2):151-60
references.pmid: 7663510
references.citation: J Am Soc Nephrol. 2000 Oct;11(10):1837-1847
references.pmid: 11004214
references.citation: Am J Kidney Dis. 1994 Oct;24(4):561-8
references.pmid: 7942810
references.citation: Clin Exp Immunol. 2006 Sep;145(3):398-406
references.pmid: 16907906
references.citation: Anal Chem. 2003 Sep 1;75(17):4646-58
references.pmid: 14632076
references.citation: Kidney Int. 2004 Jun;65(6):2018-29
references.pmid: 15149315
references.citation: Science. 1996 May 31;272(5266):1339-42
references.pmid: 8650545
references.citation: Hepatology. 1990 Apr;11(4):557-65
references.pmid: 1970324
references.citation: J Am Soc Nephrol. 2002 Oct;13(10):2508-16
references.pmid: 12239239
references.citation: J Am Soc Nephrol. 1992 Oct;3(4):984-94
references.pmid: 1333294
references.citation: J Cell Biol. 2000 Apr 3;149(1):111-24
references.pmid: 10747091
references.citation: Cell. 2007 Sep 21;130(6):1108-19
references.pmid: 17889653
references.citation: Kidney Int. 2005 Aug;68(2):603-10
references.pmid: 16014037
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Feb 17;832(1):41-6
references.pmid: 16414315
references.citation: Nat Cell Biol. 2003 Apr;5(4):287-93
references.pmid: 12669082
references.citation: J Lab Clin Med. 1994 Sep;124(3):386-94
references.pmid: 8083581
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13368-73
references.pmid: 15326289
references.citation: Anal Bioanal Chem. 2007 Oct;389(4):1017-31
references.pmid: 17668192