MicroRNA regulation of smooth muscle gene expression and phenotype

Abstract

Purpose of review: In this review, we summarize the recent advances regarding microRNA (miRNA) functions in the regulation of vascular smooth muscle cell (VSMC) differentiation and phenotypic modulation.

Recent findings: Multiple miRNAs are found to be responsible for VSMC differentiation and proliferation under physiological or pathological condition. A single miRNA downregulates multiple targets, whereas a single gene is regulated by multiple miRNAs to modulate a specific aspect of VSMC phenotype.

Summary: The phenotype of VSMCs is dynamically regulated in response to environmental stimuli. Deregulation of phenotype switching is associated with vascular diseases. Several miRNAs have been found to be highly expressed in the vasculature, to modulate VSMC phenotype, and to be dysregulated in vascular diseases. By regulating mRNA and/or protein levels posttranscriptionally, miRNAs provide a delicate regulation in the complex molecular networks that regulate the vascular system. Understanding the functions of miRNAs in the regulation of VSMC differentiation and phenotype switching provides new insights into the mechanisms of vascular development, function, and dysfunction.

Figure 1. Schematic diagram of miRNA biogenesis

miRNAs are transcribed by RNA polymerase II (RNA Pol II) as pri-miRNAs. The Drosha complex processes the pri-miRNAs into hairpin-structured pre-miRNAs. The pre-miRNAs are exported from the nucleus to the cytoplasm and are cleaved by the Dicer complex into miRNA-miRNA* duplexes. The mature miRNA is incorporated into the RISC complex and mediates post-transcriptional repression of target mRNA by translational repression and/or deadenylation and degradation.

Figure 2. Schematic diagram of VSMC phenotype modulation

In response to extracellular signals, the expression of a cohort of miRNAs is modulated. Each miRNA is implicated in contractile or synthetic phenotype regulation, and thus VSMCs can switch between phenotypes.

Figure 3. A network of miRNAs and their targets implicated in VSMC phenotype modulation

Characteristics of VSMC, such as migration, proliferation, and differentiation, are regulated by miRNAs through repression of their targets. Validated targets of each miRNA involved in VSMC phenotype modulation are indicated.