Rong Li Lab Identifies a Protein Involved in the Development of Renal Cysts

Kansas City, Mo. (February 24, 2010) – The Rong Li Laboratory has implicated histone deacetylase 5 (HDAC5) in the development of renal cysts. The work entitled “Polycystin-dependent fluid flow sensing targets histone deacetylase 5 to prevent the development of renal cysts” was published online today in the journal Development.

     Autosomal dominant polycystic kidney disease (PKD) is caused by mutations in PKD1, a GPCR-like protein, or PKD2, a TRP calcium channel physically associated with PKD1. The Li Laboratory developed an experimental system for analyzing expression patterns induced by fluid flow over epithelial cells and identified genes whose expression depends upon PKD1. Two of the genes identified, HDAC5 and myocyte enhancer factor 2C (MEF2C), have previously been shown to be involved in cardiac hypertrophy.  At the protein level, the Li Laboratory showed that HDAC5 phosphorylation and nuclear export are stimulated by exposing cells to fluid flow and that reduction in PKD1 function inhibits HDAC5 phosphorylation and export.  The Li Laboratory went on to show that knocking out HDAC5 decreases cyst volume in a PKD2 background.  Furthermore, treatment of PKD2 mutant mice with trichostatin, an HDAC inhibitor, similarly reduced cyst volume.

     The Li Laboratory’s findings are significant in suggesting the involvement of a common pathway in kidney disease and heart failure and also providing evidence that inhibition of HDAC5 or its downstream targets may have potential for treating PKD.

     Sheng Xia, a postdoc in the Li Laboratory, and Xiaogang Li, a former postdoc, were the first and second authors of the paper.  Teri Johnson of Histology and Chris Seidel, Research Advisor, also contributed to the paper, as did Darren Wallace of the University of Kansas Medical Center.