Dysregulated Krϋppel-like factor (KLF) gene expression appears in many disease-associated pathologies. In this review, we discuss physiological functions of KLFs in the kidney with a focus on potential pharmacological modulation/therapeutic applications of these KLF proteins. KLF2 is critical to maintaining endothelial barrier integrity and preventing gap formations and in prevention of glomerular endothelial cell and podocyte damage in diabetic mice. KLF4 is renoprotective in the setting of AKI and is a critical regulator of proteinuria in mice and humans. KLF6 expression in podocytes preserves mitochondrial function and prevents podocyte apoptosis, while KLF5 expression prevents podocyte apoptosis by blockade of ERK/p38 MAPK pathways. KLF15 is a critical regulator of podocyte differentiation and is protective against podocyte injury. Loss of KLF4 and KLF15 promotes renal fibrosis, while fibrotic kidneys have increased KLF5 and KLF6 expression. For therapeutic modulation of KLFs, continued screening of small molecules will promote drug discoveries targeting KLF proteins.
Keywords: Fibrosis; Interstitial inflammation; Kidney disease; Krϋppel-like factors (KLFs); Podocytes; Renal tubule cells.
Copyright © 2019. Published by Elsevier B.V.