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Decreased Renal and Urinary Neprilysin Protein Expression in db/db Mice
Author(s) -
Chodavarapu Harshita,
Bradshaw Melissa,
Salem Esam,
Elased Khalid
Publication year - 2012
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.26.1_supplement.1051.5
Subject(s) - endocrinology , medicine , neprilysin , diabetic nephropathy , nephropathy , diabetes mellitus , pathogenesis , microalbuminuria , urinary system , albuminuria , kidney , chemistry , biochemistry , enzyme
The renin angiotensin system (RAS) plays a pivotal role in the pathogenesis of diabetic nephropathy. Neutral endopeptidase or neprilysin (NEP) belongs to the M13 family of zinc‐containing metallopeptidases which converts Ang I to Ang (1–7). Ang (1–7) is a potential target in renal pathology because of its opposing effects on Ang II induced actions. The possible involvement of NEP in diabetic renoprotection has not been investigated; therefore, the aim of this study is to examine the role of neprilysin in the pathogenesis of diabetic nephropathy in db/db mice. db/db mouse model for type 2 diabetes was used to study the effect of diabetes on renal and urinary NEP. These mice exhibit hyperglycemia, hypertension, hyperinsulinemia, obesity and microalbuminuria. Urine was collected over 24 hours from db/db and lean control mice to measure the urinary albumin, creatinine and total protein. Our results showed that db/db mice were hyperglycemic and demonstrated an early onset of microalbuminuria. Western blot analysis revealed decreased renal and urinary NEP protein expression in db/db mice compared to lean control mice ( p <0.05). Immunohistochemical staining of kidney sections revealed a decrease in NEP protein expression in the db/db mice. In conclusion, downregulation of NEP could play an important role in the development of diabetic nephropathy in db/db mice. Supported by the American Heart Association.