Predictive significance of kidney myeloid-related protein 8 expression in patients with obesity- or type 2 diabetes-associated kidney diseases

• Published in: PloS one 2014-02, Vol.9 (2), p.e88942-e88942
• Main Authors: Kuwabara, Takashige, Mori, Kiyoshi, Kasahara, Masato, Yokoi, Hideki, Imamaki, Hirotaka, Ishii, Akira, Koga, Kenichi, Sugawara, Akira, Yasuno, Shinji, Ueshima, Kenji, Morikawa, Takashi, Konishi, Yoshio, Imanishi, Masahito, Nishiyama, Akira, Nakao, Kazuwa, Mukoyama, Masashi
• Format: Article
• Language: English
• Subjects: Adult; Analysis; Animals; Biology; Biopsy; Blood; Blood pressure; Calgranulin A - genetics; Calgranulin A - metabolism; Creatinine; Development and progression; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - complications; Diabetes therapy; Diabetic nephropathies; Diabetic nephropathy; Female; Fibrosis; Gene expression; Gene Expression Regulation; Genes; Hospitals; Humans; Hyperglycemia; Hypertension; Immune system; Immunohistochemistry; Inflammation; Kidney - metabolism; Kidney diseases; Kidney Diseases - complications; Kidney Diseases - diagnosis; Kidney Diseases - metabolism; Kidney Diseases - urine; Kidney transplantation; Macrophages; Macrophages - metabolism; Male; Medical research; Medical schools; Medicine; Middle Aged; mRNA; Multivariate analysis; Nephrology; Nephropathy; Obesity; Obesity - complications; Patients; Polymerase chain reaction; Prognosis; Proteins; Proteinuria; Regression analysis; Risk analysis; Risk factors; RNA; Rodents; Science; Signaling; TLR4 protein; Toll-like receptors; Tubules; Type 2 diabetes; University graduates
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0088942

We 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. In 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. Kidney 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