Table 1.

Summary of the studies associated with SRF/cofactors interaction in different diseases.

S/N	Model	Function	Mechanism	Outcome	Reference
1	Cardiac fibroblasts isolated from young adult male Sprague Dawley rats.	Anti‐apoptosis and resistance to oxidative injury	ERK1/2 MAPK‐activated SRF	Activation of DDR2‐mediated ERK1/2 MAPK regulates cell survival and cell cycle progression in cardiac fibroblasts via SRF	[42]
2	Human hepatocellular carcinoma (HCCs)	Liver cancer	Transcription of the MDM 4 oncogene	SRF, ELK1, and ELK4 were reported to be putative transcription factors binding to the MDM 4 promoter region and were associated with reduced survival of HCC patients following liver resection.	[43]
3	SRF (‐/‐) embryonic stem cells	Cell migration	Actin cytoskeletal structure	Downregulation of FA proteins in ES cells lacking SRF led to inefficient activation of the FA signaling kinase FAK and reduced overall actin expression levels in Srf (‐/‐) ES cells. These changes were accompanied by an offset treadmilling equilibrium, resulting in lowered F‐actin levels.	[57]
4	SRF knockout mice (cardiomyocytes and SMCs)	Cardiovascular development (growth and muscle differentiation)	Actin contractile and cytoskeletal structure	SRF mutant mice displayed structural defects in the heart and vasculature which coincided with decreases in SRF‐dependent gene expression and death.	[5]
5	SRF mutant mice	Skeletal muscle development	Actin cytoskeletal muscle growth and maturation	SRF deletion resulted in formation of muscle fibers without hypertrophic growth after birth leading to death during the perinatal period from severe skeletal muscle hypoplasia.	[64]
6	SRF‐f/f mice	Axon growth in mammalian brain	GSK‐3‐activated SRF phosphorylation	Phosphorylation and activation of SRF by GSK‐3 that is critical for SRF‐dependent axon growth in mammalian central neurons.	[65]
7	SRFf/f mice	Axon and neuron development	Actin cytoskeleton	SRF mutant mice exhibited deficits in cortical axonal projections with a variable loss of the corpus callosum. The number of proliferative cells in the ventricular zone increased during development. These changes were also observed in the developing excitatory neurons of neocortex and hippocampus.	[66]
8	SMC‐restricted Srf‐inducible knockout mice	Anti‐apoptosis	SRF‐dependent miRNAs	Mice exhibited severe degeneration of SMCs with reduced expression of apoptosis‐associated miRNAs, high level of SMC death, and myopathy in the intestinal muscle layers. These suggest that SMC degeneration via anti‐apoptotic miRNA deficiency resulting from SRF deficiency may be responsible.	[61]
9	Cross‐sectional study of CTD patients	Heart development	Impaired SRF transcription	Two novel mutations of SRF were identified in the DNA from the peripheral leukocyte cells. There were no differences between the mutants and wild‐type SRF in their protein expression and mRNA transcription. However, both SRF mutants had impaired SRF transcriptional activity at the SRF promoter and atrial natriuretic factor (ANF) promoter as well as reduced synergism with GATA4.	[29]
10	SHR and WKY rats	Aortic VSMC stiffening	Extracellular dysregulation (integrin β1 and BMP1/LOX via SRF/myocardin signaling)	Reconstituted vessel segments from SHR VSMCs were stiffer, had different morphologies, and less adaptable to stretch than WKY VSMCs. Also, SHR VSMCs had increased synthesis of collagen and induced collagen in reconstituted vessels in addition to higher levels of active integrin β1 and bone morphogenetic protein 1 (BMP1)‐mediated proteolytic cleavage of lysyl oxidase (LOX). These changes were attenuated by an SRF/myocardin.	[79]
11	Alzheimer’s disease patients	Cognitive decline and dementia in Alzheimer’s Disease	SRF/myocardin overexpression	There was overexpression of several SRF/myocardin‐regulated contractile proteins with hypercontractile phenotype in AD VSMC. Also, overexpression of myocardin in control human cerebral VSMC caused an AD‐like hypercontractile phenotype and reduced endothelial‐dependent and endothelial‐independent relaxation in the mouse aorta ex vivo. However, silencing SRF normalized and reversed these changes.	[82]
12	Intestinal cells and human colon cell line	Tumorigenesis	Alternatively spliced variants and isoforms of SRF	Full‐length SRF was discovered to be the predominant form of SRF in all 3 cells used (rat IEC‐6 cells, normal human colonic mucosa, and HT‐29 cells). However, the colon cancer cell lines from poorly differentiated tumors had SRFΔ5 as the predominant isoform expressed. IEC‐6 cells transfected with SRFΔ5 also had higher survival than the parental cells	[84]