Epigenetics and diabetes: understanding the mechanisms that can impact disease progression

Epigenetics is at forefront of experimental understanding of gene expression disruption by environmental influences via post-translation modification of the DNA .  More precisely, modification to the DNA packaging proteins, histones is being investigated.  Histone deacetylase (HDAC)-2 has been implicated recently in the progression of several pathological conditions such as cancer, cardiac hypertrophy and chronic pulmonary diseases.  HDAC acts via decreased acteylation of gene transcription resulting in transcriptional repression.  Although diabetic nephropathy is the most common cause of chronic kidney disease in the Western world, the molecule basis underlying the pathophysiology of diabetic nephropathy is still not entirely understood.  Noh and colleagues (2009) aimed to determine the effect of HDAC inhibition in diabetic kidney, identify the isoforms of HDAC participating in this process and examine the role of reactive oxygen species (ROS) as a downstream signaling molecule mediating diabetes of TGF-beta1-induced dysregulation of HDAC.

Their findings suggest that HDAC-2 plays an important role in the development of extracellular matrix accumulation and epithelial-to-mesenchymal transition in diabetic kidney, both hallmarks of diabetic nephropathy and that ROS mediate TGF-beta1-induced activation of HDAC-2.  These results help strengthen the notion that HDAC may play an important role in the pathogenesis of diabetic nephropathy and may lead to improved understanding of the beneficial effects of HDAC inhibitions for treatment. 

Jennifer Bridge (41005624)