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Kidney Int. 2018 Aug;94(2):259-267. doi: 10.1016/j.kint.2018.01.025. Epub 2018 Apr 21.

Are Pax proteins potential therapeutic targets in kidney disease and cancer?

Author information

1
Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
2
Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: dressler@umich.edu.

Abstract

Pax genes encode developmental regulators that are expressed in a variety of tissues and control critical events in morphogenesis. In the kidney, Pax2 and Pax8 are expressed in embryonic development and in specific renal diseases associated with aberrant epithelial cell proliferation. Prior genetic and cell biological studies suggest that reducing the activity of Pax proteins in renal cancer or in polycystic kidney disease can slow the progression of these conditions. The Pax proteins may be critical for providing tissue and locus specificity to recruit epigenetic modifiers that control gene expression and chromatin structure. Although they are nuclear, targeting Pax proteins to inhibit function may be feasible with small molecules. Such inhibition of Pax protein function may provide novel therapies for subsets of renal disorders that are tissue- and cell type-specific and avoid systemic effects on non-Pax-expressing cells and tissues. Given the paucity of effective treatments for renal cancer and cystic disease, the Pax family of proteins represents new pharmaceutical targets that merit exploration and further development.

KEYWORDS:

Pax2; Pax8; drug development; polycystic kidney disease; renal cancer; renal epithelia

PMID:
29685496
PMCID:
PMC6054895
[Available on 2019-08-01]
DOI:
10.1016/j.kint.2018.01.025

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