Serum response factor promotes re-epithelialization and muscular structure restoration during gastric ulcer healing☆

Chai, Jianyuan; Baatar, Dolgor; Tarnawski, Andrzej S.

doi:10.1053/j.gastro.2004.03.021

Cited by 44 publications

(75 citation statements)

References 27 publications

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“…72 Similarly, SRF level is elevated in an experimental model of esophageal ulceration. 73 Overexpression of SRF in a rat model of gastric/esophageal ulceration caused an amelioration of the condition with increased re-epithelialization and submucosal SMC regeneration.…”

Section: Gastrointestinal Tractmentioning

confidence: 96%

“…73 Overexpression of SRF in a rat model of gastric/esophageal ulceration caused an amelioration of the condition with increased re-epithelialization and submucosal SMC regeneration. 72,73 This healing of the ulcer appears to be a function of the activation of growth-related genes by SRF and subsequent proliferation of epithelial cells, SMCs, and myofibroblasts. Conversely, reductions of SRF in experimental models of ulceration, using antisense RNA, resulted in impaired angiogenesis of the microvasculature, presumably because of defective vascular endothelial growth factor-dependent signaling.…”

Section: Gastrointestinal Tractmentioning

confidence: 99%

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Role of serum response factor in the pathogenesis of disease

Miano

2010

Laboratory Investigation

123

100

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Serum response factor (SRF) is a ubiquitously expressed transcription factor that binds to a DNA cis element known as the CArG box, which is found in the proximal regulatory regions of over 200 experimentally validated target genes. Genetic deletion of SRF is incompatible with life in a variety of animals from different phyla. In mice, loss of SRF throughout the early embryo results in gastrulation defects precluding analyses in individual organ systems. Genetic inactivation studies using conditional or inducible promoters directing the expression of the bacteriophage Cre recombinase have shown a vital role for SRF in such cellular processes as contractility, cell migration, synaptic activity, inflammation, and cell survival. A growing number of experimental and human diseases are associated with changes in SRF expression, suggesting that SRF has a role in the pathogenesis of disease. This review summarizes data from experimental model systems and human pathology where SRF expression is either deliberately or naturally altered. Genomic DNA is a quaternary code comprising proteincoding and non-protein-coding sequences. While the protein-coding sequences are well-defined and increasingly understood, we are only beginning to elucidate the hidden information within the vast landscape of the non-proteincoding sequences. The field of comparative genomics has facilitated the identification of transcription factor-binding sites (TFBS) and microRNAs (miRs), which, aside from repetitive DNA sequences, are among the more easily decipherable non-protein-coding sequences in the human genome. Together, TFBS and miRs have essential roles in cell fate determination and cellular homeostasis of most life forms. Sequence variations (eg, single-nucleotide polymorphisms, SNPs) in the TFBS, miRs, and miR target sequences alter gene/protein expression and thus disturb homeostasis leading to disease. 1-4 A major imperative, therefore, is decoding the non-protein-coding genome relating to gene regulation to gain a full understanding of how DNA-binding transcription factors and the estimated one million or more TFBS direct normal biological processes.Serum response factor (SRF) is the founding member of the MADS-box family of transcription factors 5 and is one of the best understood DNA-binding proteins in the human proteome. The DNA-binding properties of SRF and its molecular cloning were first defined in the laboratory of Richard Treisman. 6,7 SRF has relatively low intrinsic transcriptional activity, but its interaction with over 60 cofactors confers strong transactivation potential in a cell-and context-specific manner. At least two major signaling pathways converge upon SRF to direct the programs of gene expression. 8,9 The classic pathway involves growth factor stimulation and mitogen-activated protein kinase signaling leading to the phosphorylation of the SRF cofactor, ELK1, and the activation of growth-related genes. 10,11 The second regulatory pathway occurs through Rho-dependent changes in actin dynamics. 12 In this pathway, si...

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Section: Gastrointestinal Tractmentioning

confidence: 96%

Section: Gastrointestinal Tractmentioning

confidence: 99%

Role of serum response factor in the pathogenesis of disease

Miano

2010

Laboratory Investigation

123

100

View full text Add to dashboard Cite

show abstract

“…This process involves many genes encoding growth factors, including epidermal growth factor, VEGF, keratinocyte growth factor, hepatocyte growth factor, platelet-derived growth factor, basic fibroblast growth factor, and angiopoietins. It has been reported that genes encoding these growth factors have an ulcer healing effect in vivo [2,[32][33][34]. Moreover, gene therapy has been tried for gastric cancer in vitro and in vivo with various therapeutic genes, namely p53 [35], FHIT [36], NK4 [37,38] and the Fas ligand [39].…”

Section: Resultsmentioning

confidence: 99%

Improved stomach selectivity of gene expression following microinstillation of plasmid DNA onto the gastric serosal surface in mice

Nishi

Fumoto

Ishii

et al. 2008

European Journal of Pharmaceutics and Biopharmaceutics

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Stomach-selective gene transfer is a promising approach as a therapeutic strategy for refractory gastric diseases. In this study, we improved the stomach selectivity of gene expression following microinstillation of naked plasmid DNA (pDNA) onto the gastric serosal surface in mice. pDNA encoding firefly luciferase was used as a reporter gene. It was confirmed that the gene expression level in the stomach 6 h after gastric serosal surface microinstillation of pDNA was significantly higher than after intragastric, intraperitoneal and intravenous administration. Regarding selectivity of gene expression, the gene expression level in the stomach after gastric serosal surface microinstillation of 1 µg/1 µL (dose/volume) pDNA was 5.7 times higher than that in the spleen. In our previous study (30 µg/30 µL), the expression level in the stomach was 2.7 times higher than that in the spleen; therefore, the selectivity was 2.1 times higher in this study. When we investigated gene expression at various pDNA solution concentrations, the ratio of the gene expression level in the stomach to that in the spleen was the highest as 1 µg/1 µL of pDNA, which was considered the optimal concentration. Information in this study is useful for further development of target organ-selective gene delivery systems.

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“…It has been reported that genes encoding these growth factors have an ulcer healing effect in vivo. 2,[30][31][32] Moreover, gene therapy has been tried for gastric cancer in vitro and in vivo with various strategies, such as transfer of suicide genes, 33 the p51A gene, 34 dominant negative insulin-like growth factor I receptor gene, 35 and RhoA and RhoC short interfering RNA. In summary, we demonstrated highly stomach-selective gene transfer following gastric serosal surface instillation of naked pDNA in rats.…”

Section: Discussionmentioning

confidence: 99%

Highly stomach-selective gene transfer following gastric serosal surface instillation of naked plasmid DNA in rats

et al. 2008

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Short titleStomach-selective gene transfer in rats 2 Background. The purpose of this study was to achieve stomach-selective gene transfer in rats by our simple and novel administration method, which is gastric serosal surface instillation of naked plasmid DNA (pDNA). Methods. Naked pDNA encoding firefly luciferase as a reporter gene was instilled onto the gastric serosal surface in male Wistar rats. As controls, we performed intraperitoneal, intragastric and intravenous administration of naked pDNA. At appropriate time intervals, we measured luciferase activities in the stomach and other tissues. Results. Gene expression in the stomach 6 h after gastric serosal surface instillation of naked pDNA (5 µg) was significantly higher than that using other administration methods. The present study is the first report on stomach-selective gene transfer following instillation of naked pDNA onto the gastric serosal surface in rats. Also, the gene expression level in the stomach 6 h after gastric serosal surface instillation of naked pDNA was markedly higher than that in other tissues. In a dose-dependent study, the gene expression level was saturated over 5 µg. Gene expression in the stomach was detected 3 h after gastric serosal surface instillation of naked pDNA. The gene expression level was peaked 12-24 h after instillation of naked pDNA, then decreased to similar level to 3 h at 48 h. Conclusions.Gastric serosal surface instillation of naked pDNA can be a highly stomach-selective gene transfer method in rats.

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Serum response factor promotes re-epithelialization and muscular structure restoration during gastric ulcer healing☆

Cited by 44 publications

References 27 publications

Role of serum response factor in the pathogenesis of disease

Role of serum response factor in the pathogenesis of disease

Improved stomach selectivity of gene expression following microinstillation of plasmid DNA onto the gastric serosal surface in mice

Highly stomach-selective gene transfer following gastric serosal surface instillation of naked plasmid DNA in rats

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