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H 2 S Therapy Improves MMP‐9 and NMDA Receptor Mediated Diabetic Renovascular Remodeling
Author(s) -
Kundu Sourav,
Pushpakumar Sathnur,
Tyagi Suresh C,
Sen Utpal
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.702.9
Subject(s) - downregulation and upregulation , vascularity , endocrinology , diabetic nephropathy , nmda receptor , medicine , matrix metalloproteinase , elastin , extracellular matrix , diabetes mellitus , chemistry , receptor , pathology , gene , biochemistry
Previously we reported that matrix metalloproteinase‐9 (MMP‐9) plays an important role in extracellular matrix (ECM) remodeling in diabetic kidney due to decreased H 2 S production by downregulation of CBS/CSE. Altered ECM resulted from NMDA‐R induction and dysregulation of connexins (Cxs). In this study, we determined whether H 2 S treatment reduces MMP‐9 induced ECM remodeling in diabetic nephropathy. Wild type (C57BL/6J), diabetic (Akita, C57BL/6J‐ Ins2 Akita ), MMP‐9 knockout (MMP‐9 −/− , M9KO) and double KO of Akita/MMP‐9 −/− (DKO) mice were treated without or with 0.05 g/L of NaHS in drinking water. Cortex blood flow, renal function, vascularity, MMP‐9, NMDA‐R, Cxs, collagen and elastin were measured. Diabetic mice showed decreased cortical blood flow and vascularity which improved with H 2 S treatment. DKO mice showed improved blood flow with H 2 S treatment. Akita and DKO mice showed low levels of CBS/CSE and thus H 2 S production. The levels of MMP‐9, NMDA‐R and Cxs‐40 and ‐43 were increased in Akita which normalized with H 2 S supplementation. DKO mice showed a decreasing trend for NMDA‐R and Cxs but the levels normalized only after H 2 S treatment. We conclude that H 2 S treatment reduces adverse diabetic renal remodeling by downregulation of MMP‐9 and NMDA‐R.