MicroRNAs and fibrosis

Abstract

MicroRNAs (miRNAs) are short noncoding RNAs that inhibit gene expression in plants and animals. miRNAs have emerged as key players in virtually all aspects of mammalian biology. Aberrant miRNA expression is observed in numerous human diseases such as diabetes, hypercholesterolemia, cancer, and tissue fibrosis. Therefore, approaches to correct miRNA expression represent the novel therapeutic strategies for these diseases. miRNAs are essential for kidney development and homeostasis. Aberrant miRNA expression is observed in the mouse models of kidney fibrosis. Three TGF-β-regulated miRNA families, miR-21, miR-200, and miR-29 have been shown to modulate renal fibrosis. miR-21, through a feed-forward loop, amplifies TGF-β signaling and promotes fibrosis. Conversely, miR-200 and miR-29 reduce fibrosis by inhibiting epithelial-to-mesenchymal transition and preventing the deposition of extracellular matrix, respectively. Inhibition of miR-21 expression or augmenting miR-29 expression prevents kidney fibrosis in mice. Aberrant miRNA expression perturbs signaling pathways that lead to progression of kidney fibrosis. Thus, miRNAs represent novel biomarkers and therapeutic targets in the treatment of kidney fibrosis.