scholarly journals Delayed liver regeneration in mice lacking liver serum response factor

2007 ◽  
Vol 292 (4) ◽  
pp. G996-G1001 ◽  
Author(s):  
M. Ujue Latasa ◽  
Dominique Couton ◽  
Claude Charvet ◽  
Aurélie Lafanechère ◽  
Jacques-Emmanuel Guidotti ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Serum Response Factor ◽  
Early Response ◽  
Mutant Mice ◽  
Response Factor ◽  
Impaired Liver ◽  
Serum Response

Various immediate early genes (IEGs) upregulated during the early process of liver regeneration are transcriptional targets of the serum response factor (SRF). We show here that the expression of SRF is rapidly induced in rodent liver after partial hepatectomy. Because the inactivation of the SRF gene in mice is embryonic lethal, the in vivo role of SRF in liver regeneration after partial hepatectomy was analyzed in mutant mice conditionally deleted for SRF in the liver. We demonstrate that SRF is not an essential factor for liver ontogenesis. However, adult mutant mice show impaired liver regeneration after partial hepatectomy, associated with a blunted upregulation of various SRF target IEGs. In conclusion, our work suggests that SRF is an early response transcription factor that may contribute to the initial phases of liver regeneration through its activation of IEGs.

scholarly journals Targeted Inactivation of Serum Response Factor in the Developing Heart Results in Myocardial Defects and Embryonic Lethality

2004 ◽  
Vol 24 (12) ◽  
pp. 5281-5289 ◽  
Author(s):  
Ara Parlakian ◽  
David Tuil ◽  
Ghislaine Hamard ◽  
Geneviève Tavernier ◽  
Daniele Hentzen ◽  
...  
Keyword(s):  
Heart Development ◽  
Serum Response Factor ◽  
Interventricular Septum ◽  
Early Response ◽  
Cardiac Differentiation ◽  
Response Factor ◽  
Transgenic Mouse Line ◽  
Serum Response

ABSTRACT Serum response factor (SRF) is at the confluence of multiple signaling pathways controlling the transcription of immediate-early response genes and muscle-specific genes. There are active SRF target sequences in more than 50 genes expressed in the three muscle lineages including normal and diseased hearts. However, the role of SRF in heart formation has not been addressed in vivo thus far due to the early requirement of SRF for mesoderm formation. We have generated a conditional mutant of SRF by using Cre-LoxP strategy that will be extremely useful to study the role of SRF in embryonic and postnatal cardiac functions, as well as in other tissues. This report shows that heart-specific deletion of SRF in the embryo by using a new βMHC-Cre transgenic mouse line results in lethal cardiac defects between embryonic day 10.5 (E10.5) and E13.5, as evidenced by abnormally thin myocardium, dilated cardiac chambers, poor trabeculation, and a disorganized interventricular septum. At E9.5, we found a marked reduction in the expression of essential regulators of heart development, including Nkx2.5, GATA4, myocardin, and the SRF target gene c-fos prior to overt maldevelopment. We conclude that SRF is crucial for cardiac differentiation and maturation, acting as a global regulator of multiple developmental genes.

scholarly journals Serum response factor is essential for synaptic maturation in the hippocampus

2020 ◽  
Author(s):  
Anna Krysiak ◽  
Matylda Roszkowska ◽  
Lena Majchrowicz ◽  
Anna Beroun ◽  
Piotr Michaluk ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Serum Response Factor ◽  
Imaging Techniques ◽  
Expression Patterns ◽  
Autism Spectrum ◽  
Response Factor ◽  
Serum Response

AbstractDisturbances of gene expression patterns that occur during brain development can severely affect signal transmission, connectivity, and plasticity—key features that underlie memory formation and storage in neurons. Abnormalities at the molecular level can manifest as changes in the structural and functional plasticity of dendritic spines that harbor excitatory synapses. This can lead to such developmental neuropsychiatric conditions as Autism spectrum disorders, intellectual disabilities, and schizophrenia. The present study investigated the role of the major transcriptional regulator serum response factor (SRF) in synapse maturation and its impact on behavioral phenotypes. Using in vitro and in vivo models of early postnatal SRF deletion, we studied its influence on key morphological and physiological hallmarks of spine development. The elimination of SRF in developing neurons resulted in a phenotype of immature dendritic spines and impairments in excitatory transmission. Moreover, using a combination of molecular and imaging techniques, we showed that SRF-depleted neurons exhibited a lower level of specific glutamate receptor mRNAs and a decrease in their surface expression. Additionally, the early postnatal elimination of SRF in hippocampal CA1 excitatory neurons caused spine immaturity and a specific social deficit that is frequently observed in autism patients. Altogether, our data suggest that the regulation of structural and functional dendritic spine maturation begins at the stage of gene transcription, which underpins the crucial role of such transcription factors as SRF. Moreover, disturbances of the postnatal expression of SRF translate to behavioral changes in adult animals.

scholarly journals Serum response factor is an essential transcription factor in megakaryocytic maturation

Blood ◽  
2010 ◽  
Vol 116 (11) ◽  
pp. 1942-1950 ◽  
Author(s):  
Stephanie Halene ◽  
Yuan Gao ◽  
Katherine Hahn ◽  
Stephanie Massaro ◽  
Joseph E. Italiano ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Serum Response Factor ◽  
Critical Role ◽  
Response Factor ◽  
Megakaryoblastic Leukemia ◽  
Serum Response ◽  
Essential Transcription Factor

Abstract Serum response factor (Srf) is a MADS–box transcription factor that is critical for muscle differentiation. Its function in hematopoiesis has not yet been revealed. Mkl1, a cofactor of Srf, is part of the t(1;22) translocation in acute megakaryoblastic leukemia, and plays a critical role in megakaryopoiesis. To test the role of Srf in megakaryocyte development, we crossed Pf4-Cre mice, which express Cre recombinase in cells committed to the megakaryocytic lineage, to SrfF/F mice in which functional Srf is no longer expressed after Cre-mediated excision. Pf4-Cre/SrfF/F knockout (KO) mice are born with normal Mendelian frequency, but have significant macrothrombocytopenia with approximately 50% reduction in platelet count. In contrast, the BM has increased number and percentage of CD41+ megakaryocytes (WT: 0.41% ± 0.06%; KO: 1.92% ± 0.12%) with significantly reduced ploidy. KO mice show significantly increased megakaryocyte progenitors in the BM by FACS analysis and CFU-Mk. Megakaryocytes lacking Srf have abnormal stress fiber and demarcation membrane formation, and platelets lacking Srf have abnormal actin distribution. In vitro and in vivo assays reveal platelet function defects in KO mice. Critical actin cytoskeletal genes are down-regulated in KO megakaryocytes. Thus, Srf is required for normal megakaryocyte maturation and platelet production partly because of regulation of cytoskeletal genes.

scholarly journals The Aging Vasculature: Glucose Tolerance, Hypoglycemia and the Role of the Serum Response Factor

2021 ◽  
Vol 8 (5) ◽  
pp. 58
Author(s):  
Hazel Aberdeen ◽  
Kaela Battles ◽  
Ariana Taylor ◽  
Jeranae Garner-Donald ◽  
Ana Davis-Wilson ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Molecular Mechanisms ◽  
Serum Response Factor ◽  
Response Factor ◽  
Homeostatic Control ◽  
Older Americans ◽  
The Subject ◽  
Serum Response

The fastest growing demographic in the U.S. at the present time is those aged 65 years and older. Accompanying advancing age are a myriad of physiological changes in which reserve capacity is diminished and homeostatic control attenuates. One facet of homeostatic control lost with advancing age is glucose tolerance. Nowhere is this more accentuated than in the high proportion of older Americans who are diabetic. Coupled with advancing age, diabetes predisposes affected subjects to the onset and progression of cardiovascular disease (CVD). In the treatment of type 2 diabetes, hypoglycemic episodes are a frequent clinical manifestation, which often result in more severe pathological outcomes compared to those observed in cases of insulin resistance, including premature appearance of biomarkers of senescence. Unfortunately, molecular mechanisms of hypoglycemia remain unclear and the subject of much debate. In this review, the molecular basis of the aging vasculature (endothelium) and how glycemic flux drives the appearance of cardiovascular lesions and injury are discussed. Further, we review the potential role of the serum response factor (SRF) in driving glycemic flux-related cellular signaling through its association with various proteins.

scholarly journals Critical Role of Serum Response Factor in Pulmonary Myofibroblast Differentiation Induced by TGF-β

2009 ◽  
Vol 41 (3) ◽  
pp. 332-338 ◽  
Author(s):  
Nathan Sandbo ◽  
Steven Kregel ◽  
Sebastien Taurin ◽  
Sangeeta Bhorade ◽  
Nickolai O. Dulin
Keyword(s):  
Serum Response Factor ◽  
Critical Role ◽  
Myofibroblast Differentiation ◽  
Response Factor ◽  
Serum Response

scholarly journals Myozap, a Novel Intercalated Disc Protein, Activates Serum Response Factor–Dependent Signaling and Is Required to Maintain Cardiac Function In Vivo

2010 ◽  
Vol 106 (5) ◽  
pp. 880-890 ◽  
Author(s):  
Thalia S. Seeger ◽  
Derk Frank ◽  
Claudia Rohr ◽  
Rainer Will ◽  
Steffen Just ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Serum Response Factor ◽  
Response Factor ◽  
Intercalated Disc ◽  
Serum Response

Functional antagonism between YY1 and the serum response factor

1992 ◽  
Vol 12 (9) ◽  
pp. 4209-4214
Author(s):  
A Gualberto ◽  
D LePage ◽  
G Pons ◽  
S L Mader ◽  
K Park ◽  
...  
Keyword(s):  
Serum Response Factor ◽  
Regulatory Element ◽  
Target Sequence ◽  
Response Factor ◽  
Basal Expression ◽  
Actin Promoter ◽  
Alpha Actin ◽  
Serum Response

The rapid, transient induction of the c-fos proto-oncogene by serum growth factors is mediated by the serum response element (SRE). The SRE shares homology with the muscle regulatory element (MRE) of the skeletal alpha-actin promoter. It is not known how these elements respond to proliferative and cell-type-specific signals, but the response appears to involve the binding of the serum response factor (SRF) and other proteins. Here, we report that YY1, a multifunctional transcription factor, binds to SRE and MRE sequences in vitro. The methylation interference footprint of YY1 overlaps with that of the SRF, and YY1 competes with the SRF for binding to these DNA elements. Overexpression of YY1 repressed serum-inducible and basal expression from the c-fos promoter and repressed basal expression from the skeletal alpha-actin promoter. YY1 also repressed expression from the individual SRE and MRE sequences upstream from a TATA element. Unlike that of YY1, SRF overexpression alone did not influence the transcriptional activity of the target sequence, but SRF overexpression could reverse YY1-mediated trans repression. These data suggest that YY1 and the SRF have antagonistic functions in vivo.

Cardiomyopathy in transgenic mice with cardiac-specific overexpression of serum response factor

2001 ◽  
Vol 280 (4) ◽  
pp. H1782-H1792 ◽  
Author(s):  
Xiaomin Zhang ◽  
Gohar Azhar ◽  
Jianyuan Chai ◽  
Pamela Sheridan ◽  
Koichiro Nagano ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Cardiac Muscle ◽  
Serum Response Factor ◽  
Interstitial Fibrosis ◽  
Weight Ratio ◽  
Heart Weight ◽  
Cardiomyocyte Hypertrophy ◽  
Response Factor ◽  
Serum Response

Serum response factor (SRF), a member of the MCM1, agamous, deficiens, SRF (MADS) family of transcriptional activators, has been implicated in the transcriptional control of a number of cardiac muscle genes, including cardiac α-actin, skeletal α-actin, α-myosin heavy chain (α-MHC), and β-MHC. To better understand the in vivo role of SRF in regulating genes responsible for maintenance of cardiac function, we sought to test the hypothesis that increased cardiac-specific SRF expression might be associated with altered cardiac morphology and function. We generated transgenic mice with cardiac-specific overexpression of the human SRF gene. The transgenic mice developed cardiomyopathy and exhibited increased heart weight-to-body weight ratio, increased heart weight, and four-chamber dilation. Histological examination revealed cardiomyocyte hypertrophy, collagen deposition, and interstitial fibrosis. SRF overexpression altered the expression of SRF-regulated genes and resulted in cardiac muscle dysfunction. Our results demonstrate that sustained overexpression of SRF, in the absence of other stimuli, is sufficient to induce cardiac change and suggest that SRF is likely to be one of the downstream effectors of the signaling pathways involved in mediating cardiac hypertrophy.

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