SRF: a seriously responsible factor in cardiac development and disease

Abstract

The molecular mechanisms that regulate embryogenesis and cardiac development are calibrated by multiple signal transduction pathways within or between different cell lineages via autocrine or paracrine mechanisms of action. The heart is the first functional organ to form during development, which highlights the importance of this organ in later stages of growth. Knowledge of the regulatory mechanisms underlying cardiac development and adult cardiac homeostasis paves the way for discovering therapeutic possibilities for cardiac disease treatment. Serum response factor (SRF) is a major transcription factor that controls both embryonic and adult cardiac development. SRF expression is needed through the duration of development, from the first mesodermal cell in a developing embryo to the last cell damaged by infarction in the myocardium. Precise regulation of SRF expression is critical for mesoderm formation and cardiac crescent formation in the embryo, and altered SRF levels lead to cardiomyopathies in the adult heart, suggesting the vital role played by SRF in cardiac development and disease. This review provides a detailed overview of SRF and its partners in their various functions and discusses the future scope and possible therapeutic potential of SRF in the cardiovascular system.

IGF2BP2, an RNA‐binding protein regulates cell proliferation and osteogenic differentiation by stabilizing SRF mRNA

“…The identified DEGs included SRF, a major transcription factor that controls embryonic development, cell growth and migration, cytoskeletal organization, and energy metabolism. As a conserved protein, SRF plays regulatory roles by recognizing SREs and further binding to target gene promoters (Deshpande et al, 2022). SRF regulated RUNX2 expression and OGD in vivo and in vitro (J. Chen et al, 2012), but that study did not examine its relationship with cell proliferation.…”

“…SRF binds to the promoter of the gene containing the SRE locus, promoting transcription of this gene (Tabuchi & Ihara, 2022). SRF, which recognizes target gene promoters via the SRE motif, is likely to modulate cell proliferation, migration, and differentiation (Deshpande et al, 2022; Tabuchi & Ihara, 2022). It remains unclear whether it is regulated by IGF2BP2 in osteoblasts.…”

“…The transcription factor serum response factor (SRF) regulates transcription. The CArG site is a conserved CC(A/T)6GG sequence, also known as the serum response element (SRE), on the DNA promoter (Deshpande et al, 2022). SRF binds to the promoter of the gene containing the SRE locus, promoting transcription of this gene (Tabuchi & Ihara, 2022).…”

“…These findings indicate that IGF2BP2 regulates cellular biological functions by modulating downstream molecule expression.The identified DEGs included SRF, a major transcription factor that controls embryonic development, cell growth and migration, cytoskeletal organization, and energy metabolism. As a conserved protein, SRF plays regulatory roles by recognizing SREs and further binding to target gene promoters(Deshpande et al, 2022). SRF regulated RUNX2 expression and OGD in vivo and in vitro (J Chen et al, 2012),.…”

SRF transcriptionally regulates the oligodendrocyte cytoskeleton during CNS myelination

“…Serum Response Factor (SRF) is a MADS box transcription factor that functions as a major transcriptional regulator of the actin cytoskeleton in diverse cell types (Miano et al, 2007) including neurons (Knoll and Nordheim, 2009), muscle (Esnault et al, 2014), and cardiac cells (Deshpande et al, 2022; Hauschka, 2001). Many of the cytoskeletal genes that are induced during oligodendrocyte differentiation (Cahoy et al, 2008; Dugas et al, 2012; Zhang et al, 2014) are known targets of SRF (Sun et al, 2006).…”