ArticlePloS one2014
Predictive significance of kidney myeloid-related protein 8 expression in patients with obesity- or type 2 diabetes-associated kidney diseases.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 11 citations in OpenAlex.
- Article
- The predictive role of serum calprotectin on mortality in hemodialysis patients with high phosphoremia.BMC nephrology · 2020Observational
- Ablation of Myeloid Cell MRP8 Ameliorates Nephrotoxic Serum-induced Glomerulonephritis by Affecting Macrophage Characterization through Intraglomerular Crosstalk.Scientific reports · 2020Article
- A Systems Biology Overview on Human Diabetic Nephropathy: From Genetic Susceptibility to Post-Transcriptional and Post-Translational Modifications.Journal of diabetes research · 2016Review
- TLR4 as a possible key regulator of pathological vascular remodeling by Ang II receptor activation.Hypertension research : official journal of the Japanese Society of Hypertension · 2015Article
- Article
Corrections and comments
- Expression of concern · 2023-01-11Conflict of Interest ·
- Expression of concern
Authors and funding
16 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveWe have reported that toll-like receptor 4 (TLR4) and one of its endogenous ligands, myeloid-related protein 8 (MRP8 or S100A8), play an important role in the progression of diabetic nephropathy in mice. The aim of this study was to evaluate significance of kidney MRP8 expression in patients with obesity- or type 2 diabetes-associated kidney diseases.
methodsIn diabetic, obese or control subjects, MRP8 mRNA and protein expression levels in renal biopsy samples were determined by real-time RT-PCR and immunohistochemistry (n = 28 and 65, respectively), and their associations with baseline and prognostic parameters were analyzed. Effects of MRP8 upon pro-inflammatory gene expressions were examined using macrophages.
resultsKidney MRP8 gene and protein expression levels were elevated in obese or diabetic groups compared to control group. Among all subjects, by univariate linear regression analysis, glomerular MRP8-positive cell count and tubulointerstitial MRP8-positive area at baseline were both, respectively, correlated not only with various known risk factors for diabetic nephropathy (such as systolic blood pressure, proteinuria and serum creatinine) but also with extent of glomerulosclerosis and tubulointerstitial fibrosis. Independent factors predicting urinary protein levels a year later were examined by multivariate analysis, and they included glomerular MRP8-positive cell count (β = 0.59, P<0.001), proteinuria (β = 0.37, P = 0.002) and systolic blood pressure (β = 0.21, P = 0.04) at baseline, after adjustment for known risk factors. MRP8 protein expression was observed in CD68-positive macrophages and atrophic tubules. In cultured mouse macrophages, MRP8 protein induced proinflammatory cytokine expressions and also triggered auto-induction of MRP8 in a TLR4-dependent manner.
conclusionsGlomerular MRP8 expression appears to be associated with progression of proteinuria in obese or type 2 diabetic patients, possibly by inducing inflammatory changes in macrophages through TLR4 signaling.
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