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Wang et al., "Angiotensin II downregulates MicroRNA-145 to regulate kruppel-like factor 4 and myocardin expression in human coronary arterial smooth muscle cells under high glucose conditions," Molecular Medicine, vol.
SRF binds to certain snippets of DNA called CArG boxes and serves as an anchor, while myocardin piggybacks along and turns on the genes to which SRF sticks.
Olson and fellow researchers focused on a molecule called Foxo4, to see whether it might control myocardin; they found that it turns off myocardin, thus allowing smooth muscle cells to stop contracting and grow.
Chow et al., "SRF and myocardin regulate LRP-mediated amyloid-beta clearance in brain vascular cells," Nature Cell Biology, vol.
NOX4 has also been described as a mediator of the differentiation of mouse embryonic stem cells into smooth muscle cells (SMC) with a positive correlation between the expression of NOX4 and SMC-specific genes (SMaA, SM22[alpha], hl-colponin, and SM-myh11) and transcription factors essential for the differentiation (serum response factor and myocardin), expression, and activation of NOX4 (which can occur through TGF-[beta]1) driving the differentiation (and maintenance of phenotype) of functional SMC from EC through [H.sub.2][O.sub.2] generation [115].
At the same time, miR-145 and miR143 cooperatively target a network of transcription factors, including KLF4, myocardin, and ELK-1 (ELK1, member of the ETS oncogene family), to promote differentiation and repress the proliferation of SMC [146], and VSMC differentiation marker genes such as SM-actin, calponin, and SM-MHC are upregulated bypremiR-145 and miR-145 mediated phenotypic modulation of VSMCs through its target gene KLF5 and its downstream signaling molecule, myocardin [147].
Structure of the MADS-box/MEF2 domain of MEF2A bound to DNA and its implication for myocardin recruitment.
Under normal conditions, phosphokinase (PKG) and myocardin activation should contract the smooth muscle cells (SMCs).
Huang et al., "Contribution of CXCR4+/ PDGFR+ progenitor cells in hypoxic alveolar arterioles muscularization: role of myocardin," Cardiovascular Research, vol.
Although stem cell transplantation has been used to stimulate vasculogenesis with favorable efficacy, the reparative capacity of MSCs decline with age, which may be enhanced by lentiviral-mediated expression of myocardin and telomerase reverse transcriptase (12) or culture expansion in media supplemented with growth factors prior to transplantation (13).
Expression of vascular miRNAs was decreased in the thoracic aorta of CKD rats compared to normal rats, with concordant changes in target genes of RUNX2, AT1R, and myocardin with no alteration in DROSHA or DICER, indicating that the low levels of expression are not due to altered intracellular processing.
In vitro studies of SMC differentiation have revealed the ability of serum response factor (SRF) and the SRF-cofactor, myocardin, to bind to and activate CArG elements of SMC marker genes is preceded and dependent on specific histone hyperacetylation, which is likely mediated by HATs [58-60].