HDACs, play important roles in kidney development


     Histone deacetylases (HDACs) regulate fundamental biological processes such as cellular proliferation, differentiation, and survival via genomic and non-genomic effects. HDACs, are classified in four classes depending on sequence identity and domain organization The previous study on HDAC mainly focuses on the roles of HDAC and its pathway in cancer, cardiac and immune disorders. However, there is evidence that HDACs regulate the progenitor cell population in the pronephric kidney of zebrafish.
     Development of the kidney involves interactions between several cell lineages and complex morphogenetic processes and grows into the adjacent metanephric mesenchyme (MM). Osr1/Eya1/Pax2/Six/Sall/WT1/Hoxd11 gene regulatory network specifies the MM and is absolutely required for expression of glial derived neurotrophic factor (GDNF) . Some studies demonstrated that HDAC1 and HDAC2 are crucial for regulating cell proliferation and are indispensable for embryo survival[1]. These data suggest that HDACs may play a important role in kidney development.
     The newest findings of Chen and his group, published in the journal JBC, showed that HDAC 1, 2 and 3 proteins are highly expressed in the embryonic kidney and are downregulated postnatally, without such appearance in cardiac and hepatic development. A genome wide microarray analysis indicated that HDAC inhibition stimulates global chromatin histone acetylation but causes selective effects on gene expression in embryonic kidneys. Further mechanism study showed that many developmental regulators are dependent on HDAC activity for their expression and that HDACi can both upregulate or repress gene trasnscription.
     In conclusion, all the results demonstrated that HDACs play important roles in nephrogenesis via differentially binding to and/or regulate different target genes.

[1]. Mol Cell 2008; 30, 61-72.
[2]. JBC Papers in Press, as Manuscript M111.248278.