Differential proteomic analysis of renal tissue in lupus nephritis using iTRAQ reagent technology

2011 ◽  
Vol 32 (11) ◽  
pp. 3537-3543 ◽  
Author(s):  
Weiguo Sui ◽  
Donge Tang ◽  
Guimian Zou ◽  
Jiejing Chen ◽  
Minglin Ou ◽  
...  
PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11872
Author(s):  
Yuanyuan Yang ◽  
Senyuan Hong ◽  
Cong Li ◽  
Jiaqiao Zhang ◽  
Henglong Hu ◽  
...  

Background Proteins are the most abundant component of kidney stone matrices and their presence may reflect the process of the stone’s formation. Many studies have explored the proteomics of urinary stones and crystals. We sought to comprehensively identify the proteins found in kidney stones and to identify new, reliable biomolecules for use in nephrolithiasis research. Methods We conducted bioinformatics research in November 2020 on the proteomics of urinary stones and crystals. We used the ClusterProfiler R package to transform proteins into their corresponding genes and Ensembl IDs. In each study we located where proteomic results intersected to determine the 20 most frequently identified stone matrix proteins. We used the Human Protein Atlas to obtain the biological information of the 20 proteins and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analysis to explore their biological functions. We also performed immunohistochemistry to detect the expression of the top five stone matrix proteins in renal tissue. Results We included 19 relevant studies for analysis. We then identified 1,409 proteins in the stone matrix after the duplicates were removed. The 20 most-commonly identified stone matrix proteins were: S100A8, S100A9, uromodulin, albumin, osteopontin, lactotransferrin, vitamin K-dependent protein Z, prothrombin, hemoglobin subunit beta, myeloperoxidase, mannan-binding lectin serine protease 2, lysozyme C, complement C3, serum amyloid P-component, cathepsin G, vitronectin, apolipoprotein A-1, eosinophil cationic protein, fibrinogen alpha chain, and apolipoprotein D. GO and KEGG analysis revealed that these proteins were typically engaged in inflammation and immune response.Immunohistochemistry of the top five stone matrix proteins in renal tissue showed that the expression of S100A8, S100A9, and osteopontin increased, while uromodulin decreased in kidney stone patients. Albumin was rarely expressed in the kidney with no significant difference between healthy controls and kidney stone patients. Conclusion Proteomic analysis revealed some common inflammation-related proteins in the kidney stone matrix. The role of these proteins in stone formation should be explored for their potential use as diagnostic biomarkers and therapeutic targets for urolithiasis.


2020 ◽  
Vol 21 (4) ◽  
pp. 1372 ◽  
Author(s):  
Eloi Garcia-Vives ◽  
Cristina Solé ◽  
Teresa Moliné ◽  
Marta Vidal ◽  
Irene Agraz ◽  
...  

Data on exosomal-derived urinary miRNAs have identified several miRNAs associated with disease activity and fibrosis formation, but studies on prognosis are lacking. We conducted a qPCR array screening on urinary exosomes from 14 patients with biopsy-proven proliferative lupus glomerulonephritis with a renal outcome of clinical response (n = 7) and non-response (n = 7) following therapy. Validation studies were performed by qRT-PCR in a new lupus nephritis (LN) cohort (responders = 22 and non-responders = 21). Responder patients expressed significantly increased levels of miR-31, miR-107, and miR-135b-5p in urine and renal tissue compared to non-responders. MiR-135b exhibited the best predictive value to discriminate responder patients (area under the curve = 0.783). In vitro studies showed exosome-derived miR-31, miR-107, and miR-135b-5p expression to be mainly produced by tubular renal cells stimulated with inflammatory cytokines (e.g IL1, TNFα, IFNα and IL6). Uptake of urinary exosomes from responders by mesangial cells was superior compared to that from non-responders (90% vs. 50%, p < 0.0001). HIF1A was identified as a potential common target, and low protein levels were found in non-responder renal biopsies. HIF1A inhibition reduced mesangial proliferation and IL-8, CCL2, CCL3, and CXCL1 mesangial cell production and IL-6/VCAM-1 in endothelial cells. Urinary exosomal miR-135b-5p, miR-107, and miR-31 are promising novel markers for clinical outcomes, regulating LN renal recovery by HIF1A inhibition.


Lupus ◽  
2019 ◽  
Vol 28 (9) ◽  
pp. 1091-1100
Author(s):  
V Foschi ◽  
D Bortolotti ◽  
A F Doyle ◽  
V Stratigou ◽  
L Stephens ◽  
...  

Background The study aimed to investigate whether HLA-G antigen is expressed in the kidneys of patients affected by lupus nephritis (LN) and whether its detection in renal biopsies could be adopted as a marker of treatment response and prognosis. Methods Thirty renal biopsies from patients with LN were selected and analyzed through immunohistochemistry. Laboratory and clinical data were retrospectively collected at baseline, 6 and 12 months and at the latest clinical appointment. A number of patients (63.3%) were treated with rituximab (RTX) +/− methylprednisolone in the induction phase. The expression of HLA-G in glomeruli, tubules and infiltrating cells was examined and compared between lupus patients who achieved either complete or partial renal response and those who did not respond to treatment. Results HLA-G staining was observed in the glomeruli of 20 of 30 samples from patients with LN. The expression of the antigen was detected in podocytes, along glomerular capillary walls, on parietal glomerular epithelial cells and within the juxtaglomerular apparatus. Seventy per cent of patients whose glomeruli expressed HLA-G achieved partial or complete response at 6 months and 75% at the latest available follow up compared with 30% and 40%, respectively, of those who did not show any expression. The pattern of staining in tubules and infiltrating cells was highly variable precluding any clinical correlation. Conclusion This study demonstrates that HLA-G is expressed in renal tissue in LN. Our retrospective data suggest that its expression could correlate with response to treatment.


2007 ◽  
Vol 6 (11) ◽  
pp. 4200-4209 ◽  
Author(s):  
Timothy J. Griffin ◽  
Hongwei Xie ◽  
Sricharan Bandhakavi ◽  
Jonathan Popko ◽  
Archana Mohan ◽  
...  

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Orthodoxia Nicolaou ◽  
Kleitos Sokratous ◽  
Zuzanna Makowska ◽  
María Morell ◽  
Aurélie De Groof ◽  
...  

2021 ◽  
pp. jrheum.210391
Author(s):  
Taro Iwamoto ◽  
Jessica M. Dorschner ◽  
Shanmugapriya Selvaraj ◽  
Valeria Mezzano ◽  
Mark A. Jensen ◽  
...  

Objective Previous studies suggest a link between high serum type I interferon (IFN) and lupus nephritis (LN). We determined whether serum IFN activity is associated with subtypes of LN and studied renal tissues and cells to understand the impact of IFN in LN. Methods 221 systemic lupus erythematosus (SLE) patients were studied. Serum IFN activity was measured by WISH bioassay. mRNA in-situ hybridization was used in renal tissue to measure expression of the representative IFN-induced gene, interferon-induced protein with tetratricopeptide repeats-1 (IFIT1), and the plasmacytoid dendritic cell (pDC) marker gene C-type lectin domain family-4 member C (CLEC4C or BDCA2). Podocyte cell line gene expression was measured by real-time PCR. Results Class III/IV LN prevalence was significantly increased in patients with high serum IFN compared with those with low IFN (OR=5.48, p=4.0x10-7). In multivariate regression models, type I IFN was a stronger predictor of class III/IV LN than complement C3 or anti-dsDNA antibody, and could account for the association of these variables with LN. IFIT1 expression was increased in all classes of LN, but most in the glomerular areas of active class III/IV LN kidneys. IFIT1 expression was not closely co-localized with pDCs. IFN directly activated podocyte cell lines to induce chemokines and proapoptotic molecules. Conclusion Systemic high IFN is involved in the pathogenesis of severe LN. We do not find co-localization of pDCs with IFN signature in renal tissue, and instead observe the greatest intensity of IFN signature in glomerular areas, which could suggest a blood source of IFN.


2011 ◽  
Vol 39 (2) ◽  
pp. 1315-1322 ◽  
Author(s):  
Gang Chen ◽  
Jing-bin Huang ◽  
Jie Mi ◽  
Yun-feng He ◽  
Xiao-hou Wu ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Qingjuan Liu ◽  
Yunxia Du ◽  
Kejun Li ◽  
Wei Zhang ◽  
Xiaojuan Feng ◽  
...  

The purpose of this study was to investigate the role of oncostatin M (OSM) in tubulointerstitial lesion (TIL) in lupus nephritis (LN). We found that OSM was highly expressed in the renal tissue of LN mice. OSM is one of the interleukin-6 cytokine family members. In order to clarify the role and mechanism of OSM in LN, mice with LN were treated with anti-OSM antibody or isotype antibody. We evaluated the tubular epithelial-mesenchymal transdifferentiation (EMT) by detecting the E-cadherin, α-smooth muscle actin (α-SMA), and fibronectin (FN) expression. We analyzed the inflammation by observing the monocyte chemotactic factor-1 (MCP-1) and intercellular adhesion molecule (ICAM-1) expression and calculated the tubulointerstitial fibrosis area by Masson staining. The results showed that anti-OSM antibody, rather than isotype antibody, improved EMT, inflammation, and tubulointerstitial fibrosis. In addition, the signal transducer and activator of transcription (STAT) 1 and STAT3 signaling was activated by tyrosine phosphorylation in LN mouse renal tissue, indicating that the phosphorylated STAT1 (p-STAT1) and p-STAT3 were involved in kidney injury. Moreover, decreased p-STAT3 instead of p-STAT1 has been observed after anti-OSM antibody injection. Thus, we concluded that OSM is associated with TIL in lupus nephritis, which may be connected with the activation of STAT3 rather than that of STAT1.


2012 ◽  
Vol 39 (5) ◽  
pp. 974-978 ◽  
Author(s):  
ZHUOLONG WANG ◽  
MENGTAO LI ◽  
XIAOFENG ZENG ◽  
XINJIAN LIU

Objective.To determine the significance of hepatitis B virus (HBV)-associated antigen deposition in renal tissue from patients with systemic lupus erythematosus (SLE).Methods.The medical records of 166 inpatients with lupus nephritis and 384 controls without SLE were analyzed retrospectively. Patients with SLE were classified as positive or negative depending on whether HBV-associated antigen deposition was detected in renal biopsies.Results.HBV-associated antigen deposition was mainly detected in renal tissue from patients with SLE (50.6%), primary renal glomerular disease (20.8%), and allergic purpura (21.7%). It was not detected in renal tissue from patients with diabetic nephropathy, hypertensive nephrosclerosis, thin basement membrane nephropathy, or Alport syndrome. Hepatitis B surface antigen and core antigen were deposited in the mesangial region and vascular loops. The positive group had a significantly higher frequency of IgG, IgA, and IgM deposition than the negative group (53.6% vs 30.5%; p < 0.01). There was no significant difference in the types of lupus nephritis observed between the 2 groups.Conclusion.There was a high prevalence of HBV-associated antigen deposition in renal tissue of patients with SLE by indirect immunofluorescence, which may result mainly from the cross-reactivity with deposited immunoglobulins.


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