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Meprin deficient mice have a more severe form of diabetic nephropathy
Author(s) -
Conley Sabena,
Han Jian,
Hurley Steven,
Ongeri Elimelda Moige
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.702.5
Subject(s) - fibronectin , laminin , diabetic nephropathy , fibrosis , extracellular matrix , medicine , streptozotocin , type iv collagen , endocrinology , blood urea nitrogen , diabetes mellitus , nephropathy , kidney , chemistry , biology , biochemistry
Diabetic nephropathy (DN) is the leading cause of end stage renal disease, and is associated with high morbidity and mortality rates. Key morphological changes observed in DN include accumulation of extracellular matrix (ECM) proteins and tubulointerstitial fibrosis. Meprins are metalloproteinases that are abundantly expressed in the brush border membranes of proximal kidney tubules. Meprins are also expressed in leukocytes (monocytes and macrophages) and podocytes. Meprins cleave ECM proteins such as collagen IV, collagen VI, fibronectin, laminin, and nidogen‐1 in vitro. Meprins could thus reverse or prevent the buildup of ECM which causes fibrosis in DN. Meprin β single nucleotide polymorphisms are also associated with DN in the Pima Indians, a Native American tribe with an extremely high rate of type 2 diabetes and DN. The objective of this study was to characterize DN in meprin deficient mice. Low dose streptozotocin was used to induce type 1 diabetes in wild‐type and meprin knockout mice on a C57BL/6 background. Additional comparisons were made in mice on a C3H/He background, which are deficient in meprin α. Mortality rates were significantly higher in diabetic meprin deficient mice. Eight week blood urea nitrogen (BUN) and the urine creatinine/albumin ratio were significantly higher in the meprin deficient mice, indicating a more severe form of DN. The results suggest that meprins protect against DN in mice.