Disease and gender-specific dysregulation of NGAL and MMP-9 in type 1 diabetes mellitus
| Autor: | Chan-Hee Jo, Kathryn M. Thrailkill, Robert C. Bunn, Cynthia S. Moreau, John L. Fowlkes, Alba E. Morales-Pozzo, Charles K. Lumpkin, Gael Cockrell |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Endocrinology Diabetes and Metabolism Gene Expression Renal function Urine Kidney Function Tests Article Nephropathy Podocyte Diabetic nephropathy Young Adult Endocrinology Lipocalin-2 Proto-Oncogene Proteins Diabetes mellitus Internal medicine medicine Albuminuria Humans Diabetic Nephropathies Sex Characteristics Tissue Inhibitor of Metalloproteinase-1 Podocytes business.industry Age Factors medicine.disease Lipocalins Diabetes Mellitus Type 1 medicine.anatomical_structure Matrix Metalloproteinase 9 Biomarker (medicine) Female medicine.symptom business Acute-Phase Proteins |
| Zdroj: | Endocrine. 37:336-343 |
| ISSN: | 1559-0100 1355-008X |
| DOI: | 10.1007/s12020-010-9308-6 |
| Popis: | Neutrophil gelatinase-associated lipocalin (NGAL), a biomarker of renal injury, can bind matrix metalloproteinase-9 (MMP-9) and inhibit its degradation, thereby sustaining MMP-9 proteolytic activity. MMP-9 is produced by renal podocytes, and podocyte MMP production can be modified by high ambient glucose levels. Moreover, dysregulation of MMP-9 activity, gene expression, or urine concentrations has been demonstrated in T2DM-associated nephropathy and in non-diabetic proteinuric renal diseases. Our objective was to determine whether NGAL/MMP-9 dysregulation might contribute to or serve as a biomarker of diabetic nephropathy in type 1 DM (T1DM). Plasma MMP-9, and urine NGAL and MMP-9 concentrations were measured in 121 T1DM and 55 control subjects and examined relative to indicators of glycemia, renal function, and degree of albuminuria. T1DM was associated with a significant increase in urinary excretion of both NGAL and MMP-9, and urine NGAL:Cr (NGAL corrected to urine creatinine) and urine MMP-9:Cr concentrations were highly correlated with each other. Both were also positively correlated with measurements of glycemic control and with albuminuria. Plasma MMP-9, urine MMP-9, and urine NGAL concentrations were significantly higher in females compared to males, and urine MMP-9:Cr concentrations displayed a menstrual cycle specific pattern. Increased urinary excretion of NGAL and MMP-9 supports a role for NGAL/MMP-9 dysregulation in renal dysfunction; moreover, gender-specific differences could support a gender contribution to pathological mechanisms or susceptibility for the development of renal complications in diabetes mellitus. |
| Databáze: | OpenAIRE |
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