Proteomic analysis of alpha‐1‐antitrypsin in immunoglobulin A nephropathy

Kwak, Noh-Jin; Wang, Eun-Hui; Heo, Il-Young; Jin, Dong-Chan; Cha, Jung-Ho; Lee, Kweon-Haeng; Yang, Chul-Woo; Kang, Chang-Suk; Choi, Yeong-Jin

doi:10.1002/prca.200600288

Cited by 13 publications

(13 citation statements)

References 59 publications

(22 reference statements)

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“…Accumulating studies have showed that AAT may lead to lung pathologies [68], type 1 diabetes [69], arthritis [70], and lupus [71]. Kwak et al [72] found that the expression of AAT is elevated in renal biopsies, while other investigators detected that it is overexpressed in the urine of some renal diseases [73–75]. This phenomenon was consistent with our result in which AAT was upregulated.…”

Section: Discussionsupporting

confidence: 92%

iTRAQ‐Based Proteomics of Chronic Renal Failure Rats after FuShengong Decoction Treatment Reveals Haptoglobin and Alpha‐1‐Antitrypsin as Potential Biomarkers

Wei

Huang

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Background. Chronic renal failure (CRF) has become a global health problem and bears a huge economic burden. FuShengong Decoction (FSGD) as traditional Chinese medicine has multiple pharmacological effects. Objectives. To understand the underlying molecular mechanism and signaling pathway involved in the FSGD treatment of CRF and screen differentially expressed proteins in rats with CRF treated with FSGD. Methods. Thirty-three male Sprague-Dawley rats were randomly divided into control group, CRF group, and FSGD group. Differentially expressed proteins were screened by iTRAQ coupled with nanoLC-MS/MS, and these identified proteins were later analyzed by GO, KEGG, and STRING. Additionally, haptoglobin (HP) and alpha-1-antitrypsin (AAT) were finally verified by ELISA, Western blot, and real time PCR. Results. A total of 417 proteins were identified. Nineteen differentially expressed proteins were identified in the FSGD group compared with the model group, of which 3 proteins were upregulated and 16 proteins were downregulated. Cluster analysis indicated that inflammatory response was associated with these proteins and complement and coagulation cascade pathways were predominantly involved. The validation methods further confirmed that the levels of HP and AAT were significantly increased. Conclusions. HP and AAT may be the important biomarkers in the pathogenesis of CRF and FSGD therapy.

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Section: Discussionsupporting

confidence: 92%

iTRAQ‐Based Proteomics of Chronic Renal Failure Rats after FuShengong Decoction Treatment Reveals Haptoglobin and Alpha‐1‐Antitrypsin as Potential Biomarkers

Wei

Huang

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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“…These explanations are speculative but are fitting at a conceptual level and have been mentioned here to highlight the significance of the human urinary database in a way that opens a door for further investigation whereby researchers of all disciplines are invited to participate. ␣ 1 -Antitrypsin and its fragments were reported to be upregulated in several types of CKD (57,63,68,69). Thus, increased urinary excretion of a fragment of this highly abundant plasma protein, together with fragments derived from serum albumin and fibrinogen, may reflect chronic renal damage.…”

Section: Table I Demographic Data Of All Patients Used In This Studymentioning

confidence: 99%

Naturally Occurring Human Urinary Peptides for Use in Diagnosis of Chronic Kidney Disease

Good

Zürbig

Argilés³

et al. 2010

Molecular & Cellular Proteomics

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Because of its availability, ease of collection, and correlation with physiology and pathology, urine is an attractive source for clinical proteomics/peptidomics. However, the lack of comparable data sets from large cohorts has greatly hindered the development of clinical proteomics. Here, we report the establishment of a reproducible, high resolution method for peptidome analysis of naturally occurring human urinary peptides and proteins, ranging from 800 to 17,000 Da, using samples from 3,600 individuals analyzed by capillary electrophoresis coupled to MS. All processed data were deposited in an Structured Query Language (SQL) database. This database currently contains 5,010 relevant unique urinary peptides that serve as a pool of potential classifiers for diagnosis and monitoring of various diseases. As an example, by using this source of information, we were able to define urinary peptide biomarkers for chronic kidney diseases, allowing diagnosis of these diseases with high accuracy. Application of the chronic kidney disease-specific biomarker set to an independent test cohort in the subsequent replication phase resulted in 85.5% sensitivity and 100% specificity. These results indicate the potential usefulness of capillary electrophoresis coupled to MS for clinical applications in the analysis of naturally occurring urinary peptides. Molecular & Cellular Proteomics 9:2424 -2437, 2010.From the Departments of a Chemistry and

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“…Kwak et al [40] reported increased levels of A1AT peptides in kidney tissue and urine in IgAN patients compared with healthy subjects. The authors speculated that renal tubular epithelial cells produce A1AT in response to tubulointerstitial damage.…”

Section: Discussionmentioning

confidence: 99%

Poor histological lesions in IgA nephropathy may be reflected in blood and urine peptide profiling

et al. 2013

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BackgroundIgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, leading to renal failure in 15% to 40% of cases. IgAN is diagnosed by renal biopsy, an invasive method that is not risk-free. We used blood and urine peptide profiles as a noninvasive method of linking IgAN-associated changes with histological lesions by Oxford classification.MethodsWe prospectively studied 19 patients with biopsy-proven IgAN and 14 healthy subjects from 2006 to 2009, excluding subjects with crescentic glomerulonephritis and collecting clinical and biochemical data at the time of diagnosis and during follow-up (24 months). Histological lesions were evaluated by Oxford classification. Proteomic analysis was performed by combining magnetic bead (MB) technology and mass spectrometry (MALDI-TOF MS) to obtain peptide profiles. Doubling of serum creatinine was considered a variable of poor renal prognosis.ResultsWe identified 55 peptides—13 in serum, 26 in plasma, and 16 in urine—that differentiated IgAN patients from healthy subjects. A significant association was noted between serum/plasma and urine peptides and histological findings—ie, tubulointerstitial damage, segmental glomerulosclerosis, and endocapillary injury.We also identified 3 peptides—corresponding to bradykinin, uromodulin, and alpha-1-antitrypsin—that were associated with severity of lesions, such as tubulointerstitial damage and segmental glomerulosclerosis.Moreover, blood peptides with m/z 2953, 5337, 9287, and 9289 and urine peptides with m/z 1769, 1898, 1913, 1945, 2491, 2756, 2977, 3004, 3389, and 4752 correlated significantly with poor renal function.ConclusionsIn patients with IgAN, the use of noninvasive approaches, such as blood and urine proteomics, can provide valuable information beyond that of standard diagnostic techniques, allowing us to identify blood and urine peptide profiles that are associated with poor histological lesions in IgAN patients.

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Proteomic analysis of alpha‐1‐antitrypsin in immunoglobulin A nephropathy

Cited by 13 publications

References 59 publications

iTRAQ‐Based Proteomics of Chronic Renal Failure Rats after FuShengong Decoction Treatment Reveals Haptoglobin and Alpha‐1‐Antitrypsin as Potential Biomarkers

iTRAQ‐Based Proteomics of Chronic Renal Failure Rats after FuShengong Decoction Treatment Reveals Haptoglobin and Alpha‐1‐Antitrypsin as Potential Biomarkers

Naturally Occurring Human Urinary Peptides for Use in Diagnosis of Chronic Kidney Disease

Poor histological lesions in IgA nephropathy may be reflected in blood and urine peptide profiling

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