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Suppression of Albumin‐Induced Matrix Metalloproteinase‐9 by Rosiglitazone in Renal Tubular Epithelial Cells
Author(s) -
Cobbs Alyssa,
Chen Xiaoming,
Khamdy Anjulyna,
Chima Ashmeer,
George Jasmine,
Zhao Xueying
Publication year - 2017
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.31.1_supplement.716.13
Subject(s) - rosiglitazone , endocrinology , albuminuria , medicine , albumin , diabetic nephropathy , kidney , matrix metalloproteinase , immunostaining , diabetes mellitus , kidney disease , chemistry , immunohistochemistry
Matrix metalloproteinase‐9 (MMP‐9) activation is closely linked to albuminuria in chronic kidney disease. This study was designed to explore the role of albumin on MMP‐9 expression and activity in renal tubular epithelial cells (TECs). The effect of rosiglitazone, a PPARγ agonist, on MMP‐9 activation was further examined in the diabetic kidneys and in vitro primary cultured TECs. In vivo, in situ zymography and immunostaining revealed an increase in gelatinase activity and MMP‐9 protein in the damaged tubules of Zucker diabetic rats. Increased tubular MMP‐9 staining was mainly observed in the tubules expressing kidney injury molecule‐1 (KIM‐1) in the diabetic kidneys. Additionally, urinary excretion of MMP‐9 was associated with an increase in urinary albumin in untreated diabetic rats. Chronic administration of rosiglitazone led to a downregulation of KIM‐1 and osteopontin genes in the diabetic kidneys. Moreover, urinary albumin and MMP‐9 protein were significantly decreased in rosiglitazone‐treated diabetic rats. To evaluate the effect of albumin on expression and activity of MMP‐9, primary cultured rat TECs were incubated with rat serum albumin (RSA, 0.1 – 0.5 mg/ml) for 24 – 48 hrs. RSA administration resulted in a dose‐dependent increase in MMP‐9 protein and activity in culture supernatants of TECs. Rosiglitazone pretreatment significantly attenuated albumin‐induced MMP‐9 expression and secretion from TECs. Taken together, these results suggest that albuminuria may accelerate kidney disease progression by activating tubular MMP‐9. The renoprotective effects exerted by rosiglitazone may be attributed partially to its suppression of albumin‐induced MMP‐9 activity in diabetic kidney disease. Support or Funding Information This work is supported by the NIH SDK096441, 1SC1DK112151, 8G12MD007602 and 8U54MD007588.