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. Author manuscript; available in PMC: 2014 Jul 7.
Published in final edited form as: J Urol. 2013 Jun 29;191(1):242–252. doi: 10.1016/j.juro.2013.06.110

Figure 8. The HDAC-Dependent Transcriptional Repression of Bmp-7 Potentiates TGF-β-Mediated Renal Fibrosis in Obstructive Uropathies.

Figure 8

The BMP-7 protein is a secreted cytokine that normally functions to stimulate gene transcription by binding to its receptor and activating the Smad1/5/8 transcription factors. The activation of the BMP-7 pathway also suppresses the pro-fibrotic TGF-β pathway by sequestering Smad4, a protein necessary for the transcription of many TGF-β-dependent genes.6 These counter-regulatory mechanisms are important for the suppression of TGF-β-dependent pro-fibrotic pathways during kidney repair.8 However, chronic urinary tract obstruction results in the HDAC-dependent suppression of Bmp-7 transcription. The loss of BMP-7 results in the dysregulation of kidney repair along with the persistent and inappropriate activation of the TGF-β pathway. Importantly, treatment with pharmacologic HDAC inhibitors restores BMP-7 expression, suppresses TGF-β-dependent signaling pathways, and prevents renal fibrosis following chronic urinary tract obstruction.