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Secretory Leukocyte Peptidase Inhibitor (SLPI) is a Novel Predictor of Tubulointerstitial Injury and Renal Outcome in Patients with Diabetic Nephropathy

ABSTRACT: Secretory Leukocyte Peptidase Inhibitor (SLPI) is a Novel Predictor of Tubulointerstitial Injury and Renal Outcome in Patients with Diabetic Nephropathy

PROVIDER: PRJNA664391 | ENA |

REPOSITORIES: ENA

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Secretory Leukocyte Peptidase Inhibitor (SLPI) is a Novel Predictor of Tubulointerstitial Injury and Renal Outcome in Patients with Diabetic Nephropathy

Project description:Tubulointerstitial injury plays an important role in diabetic nephropathy (DN) progression; however, no reliable urinary molecule has been used to predict tubulointerstitial injury and renal outcome of DN clinically. In this study, based on tubulointerstitial transcriptome, we identified secretory leukocyte peptidase inhibitor (SLPI) as the molecule associated with renal fibrosis and prognosis of DN. In tubular cells, high glucose could upregulate SLPI, which bound with β-catenin and GSK-3β reciprocally, abolished the interaction between β-catenin and GSK-3β, diminished GSK-3β-regulated β-catenin phosphorylation and the subsequent ubiquitination and degradation, thus led to β-catenin signaling activation and renal fibrosis. Db/db mice injected with adenovirus carrying Slpi-3xflag-GFP (Ad-Slpi-GFP) developed β-catenin signaling activation in the proximal tubule, worse albuminuria and tubulointerstitial fibrosis. Conversely, Slpi knockout (KO) mice with STZ-induced DN developed less albuminuria, tubulointerstitial fibrosis and β-catenin signaling activation. Furthermore, clinical studies showed that urinary SLPI protein level (uSLPI/Cr) had significant correlation with intrarenal SLPI mRNA and interstitial fibrosis. In an independent prospective cohort enrolled 711 patients with biopsy proven DN, uSLPI/Cr level was significantly associated with eGFR slope and improved the prediction value of renal outcome. Together, our study identified SLPI as a novel critical regulator for the progression of tubulointerstitial injury, which may be used as an independent risk predictor of DN progression.

2022-08-03 | GSE158230 | GEO

An atypical parvovirus driving chronic tubulointerstitial nephropathy and kidney fibrosis

Project description:The occurrence of a spontaneous nephropathy in laboratory mice, characterized by tubular degeneration and intranuclear inclusions, has puzzled pathologists for over four decades. While the condition takes a more severe course in immunodeficient animals suggesting an infectious cause, its etiology has remained elusive. Using an unbiased metagenomics approach, we have identified the causative agent as a novel virus, mouse kidney parvovirus (MKPV), belonging to a divergent and unclassified genus of the Parvoviridae. MKPV was found to be present in animal facilities in Australia and North America, is transmitted via the orofecal route and is controlled by the adaptive immune system. Detailed analysis of the clinical course and histopathologic features demonstrated a stepwise progression of pathology ranging from sporadic tubular inclusions to extensive tubular degeneration and interstitial fibrosis culminating in renal failure. In summary, we identify a novel, widely distributed pathogen in laboratory mice causing significant impact on the interpretation and outcome of biomedical research based on mouse models. Additionally, we establish MKPV-induced nephropathy as a new tool for elucidating the mechanisms of tubulointerstitial fibrosis that shares molecular features with chronic kidney disease in humans.

2018-09-06 | PXD010540 | Pride

Tubulointerstitial RNAseq counts from adults in the Neptune Cohort

Project description:Tubulointerstitial Transcriptome in the Neptune Cohort

2022-04-15 | GSE182380 | GEO

Transcriptome analysis of tubulointerstitial tissues of patients with focal segmental glomerulosclerosis

Project description:Transcriptome comparison of tubulointerstitial tissues from kidneys with focal segmental glomerulosclerosis (FSGS) and tubulointerstitial tissues from the unaffected portion of surgical nephrectomies. High-density Affymetrix Human Transcriptome Arrays (HTA) 2.0 were used for the gene expression analysis.

2019-01-29 | GSE125779 | GEO

Dipeptidyl peptidase-IV is associated with decreased glioma growth

Project description:Effect of expression of dipeptidyl peptidase-IV (DPP-IV) in U373 cell line on uncontrolled cell proliferation and aberrant interactions with the brain extracellular matrix.

2011-12-31 | E-MTAB-583 | biostudies-arrayexpress

Gene expression profiling of genes differentially expressed by oral carcinoma Ca9-22 and SLPI-deficient Ca9-22 (ÎSLPI) cells

Project description:We used the myoma model in conjunction with gene expression profiling with microarray data as an efficient tool for high throughput analysis and to screen for differentially expressed genes. Our aim was to identify candidates playing an important role in SLPI and/or MMP-promoted tumor invasion by comparing oral carcinoma Ca9-22 cells, which highly express secretory leukocyte protease inhibitor (SLPI) gene, with SLPI-deficient Ca9-22 cells. In oral carcinoma Ca9-22 and SLPI-deficient Ca9-22 (ÎSLPI) samples, gene expression profiling was performed with the Affymetrix Human Genome U133 Plus 2.0 Array. Two arrays for 2 cell lines were analyzed.

2016-08-22 | E-GEOD-78501 | biostudies-arrayexpress

Tubulointerstitial transcriptome from ERCB subjects with chronic kidney disease and living donor biopsies.

Project description:Tubulointerstitial transcriptome from ERCB subjects with chronic kidney disease and living donor biopsies. Samples included in this analysis have been previously analyzed using older CDF definitions and are included under previous GEO submissions - GSE47184 (chronic kidney disease samples), and GSE32591 (IgA nephropathy samples). RNA from the tubulointerstitial compartment of was extracted and processed for hybridization on Affymetrix microarrays, annotated using Human Entrez Gene ID custom CDF version 19. This dataset is part of the TransQST collection.

2018-01-24 | E-GEOD-104954 | biostudies-arrayexpress

Veterinary trypanocidal benzoxaboroles are peptidase-activated prodrugs

Project description:Veterinary trypanocidal benzoxaboroles are peptidase-activated prodrugs

| PRJEB34627 | ENA

Gene expression profiling of genes differentially expressed by oral carcinoma Ca9-22 and SLPI-deficient Ca9-22 (ΔSLPI) cells

2016-08-22 | GSE78501 | GEO

A lack of secretory leukocyte protease inhibitor (SLPI) causes defects in granulocytic differentiation.

Project description:Expression data from CD34+ hematopoietic cells transduced with control or anti-SLPI shRNA, serum starved and treated with G-CSF. CD34+ hematopoietic cells were isolated from the bone marrow of healthy individuals, transduced with lenitvirus-based RFP-expressed shRNA constructs targeting SLPI mRNA or scrambled control shRNA. After 3 days of the transductions, RFP+ cells were sorted, serum starved for 24 hours and treated with G-CSF 10 ng/ml for 18 hours. Total RNA of sorted cells was isolated and used for Affymetrix Exome arrays.

2014-03-04 | E-GEOD-53353 | biostudies-arrayexpress

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