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Histone deacetylase 2 plays an important role in the development and progression of diabetic renal injury
Author(s) -
Oh Eun Young,
Noh Hyunjin,
Seo Ji Yeon,
Yu Mi Ra,
Lee Hi Bahl,
Ha Hunjoo
Publication year - 2008
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.22.1_supplement.944.5
Subject(s) - trichostatin a , histone deacetylase , diabetic nephropathy , downregulation and upregulation , fibrosis , kidney , cancer research , gene silencing , hdac6 , extracellular matrix , hdac3 , kidney disease , medicine , microbiology and biotechnology , chemistry , endocrinology , histone , biology , biochemistry , gene
Diabetic nephropathy is the leading cause of end‐stage renal disease and characterized by excessive accumulation of extracellular matrix (ECM) in the kidney. The role of epithelial‐mesenchymal transition (EMT) in the development of renal fibrosis is well known. Histone deacetylase (HDAC) inhibitors have been shown to exert antifibrotic effect but the role of HDAC in diabetic renal injury remains incompletely understood. Here we demonstrate that trichostatin A (TSA), a nonselective HDAC inhibitor, prevents albuminuria, EMT, and enhanced ECM expression in streptozotocin‐induced diabetic rat kidney without significant effect on blood glucose. Hyperacetylation of histone (H3 and H4) by TSA is associated with downregulation of ECM mRNAs and reversal of EMT in TGF‐β1‐stimulated normal rat kidney tubular epithelial (NRK52E) cells. TGF‐β1 significantly increases activity of HDAC 2, a class I HDAC, and HDAC 2 silencing using small interference RNA represses TGF‐β1‐induced ECM upregulation and EMT in NRK‐52E cells. These results support an important role for HDAC 2 in the development and progression of renal fibrosis and suggest HDAC 2 as a novel therapeutic target for the attenuation of diabetic renal injury. (Supported by R01‐2006‐000‐10829‐0s and R15‐2006‐020 from KOSEF and BK 21)