Abstract
MicroRNAs (miRNAs or miRs) have emerged as key regulators of gene expression in essential cellular processes, such as cell growth, differentiation and development. Recent findings have established that the levels of miRNAs are modulated by cell signaling mechanisms, including the bone morphogenetic protein (BMP) signaling pathway. The BMP signaling pathway controls diverse cellular activities by modulating the levels of miRNAs, indicating the complexity of gene regulation by the BMP signaling pathway. The tight regulation of the levels of miRNAs is critical for maintaining normal physiological conditions, and dysregulated miRNA levels contribute to the development of diseases. In the present review, we discuss different insights (provided over the past decade) into the regulation of miRNAs governed by the BMP signaling pathway and the implications of this regulation on the understanding of the cellular differentiation of vascular smooth muscle cells (VSMCs), osteoblasts and neuronal cells.
Highlights
The inactivation of the bone morphogenetic protein (BMP) signaling pathway has been shown to result in the development of vascular disorders [11]
The regulation of miRNA-96 expression by BMP signaling is critical for the modulation of the vascular smooth muscle cells (VSMCs) phenotype [18]. miRNA-96 is downregulated by BMP4 in VSMCs, which results in the suppression of a novel target, Tribbles-like protein 3 (Trb3)
BMP signals activate the transcription of the miRNA-143/145 gene cluster through a consensus sequence termed the CArG box by serum response factor (SRF) and myocardin/myocardinrelated transcription factor (MRTF)-A. miRNA-143/145 promote the contractile phenotype of VSMCs by regulating the expression of smooth muscle cell (SMC)-specific genes and cytoskeletal dynamics and by inhibiting the proliferation of VSMCs. miRNA-143/145 repress multiple targets, including Kruppel-like factor 4 (KLF4), which is antagonistic to VSMC differentiation [22]
Summary
The inactivation of the BMP signaling pathway has been shown to result in the development of vascular disorders [11]. BMP signaling increases the expression of smooth muscle cell (SMC)-specific contractile genes and inhibits cell proliferation and migration, leading to the differentiation of VSMCs [13]. BMP signaling downregulates transcription of the miRNA-302~367 gene cluster in various types of cells, including VSMCs [20] This transcriptional repression of miRNA-302 by BMP signaling is mediated by Smads. MiRNA-143/145 promote the contractile phenotype of VSMCs by regulating the expression of SMC-specific genes and cytoskeletal dynamics and by inhibiting the proliferation of VSMCs. miRNA-143/145 repress multiple targets, including Kruppel-like factor 4 (KLF4), which is antagonistic to VSMC differentiation [22]. A microarray analysis demonstrated that BMP2 decreases miRNA-30b and miRNA-30c expression, leading to the promotion of VSMC calcification [23] This downregulation of miRNA-30b and miRNA-30c is mediated by a Smad-independent pathway. The downregulation of miRNA‐30b/c by BMP signaling is sufficient to increase Runx expression, which in turn results in the increased expression of the Runx2-dependent genes, osteopontin and osteocalcin, increased intracellular calcium deposition and the calcification of VSMCs [23]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
