Differential modulation of gene expression among rat tissues with warm ischemia

Miyatake, Yukiko; Ikeda, Hitoshi; Michimata, Rie; Koizumi, Seiko; Ishizu, Akihiro; Nishimura, Norihiro; Yoshiki, Takashi

doi:10.1016/j.yexmp.2004.07.004

Cited by 32 publications

(25 citation statements)

References 27 publications

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“…69 cDNA array analysis further showed that Egr-1 mRNA levels in rat lungs increase 5-fold 1 hour after warm ischemia following surgical extirpation compared with controls. 70 Chronic exposure (14 days) of newborn calves to 12%, rather than 21%, O 2 upregulates Egr-1 protein expression in pulmonary artery adventitial fibroblasts. Hypoxia (1%) induces Egr-1 expression and DNA synthesis in fibroblasts cultured from hypoxic animals, after 6 and 24 hours, respectively.…”

Section: Hypoxia and Ischemiamentioning

confidence: 99%

Early Growth Response-1 in Cardiovascular Pathobiology

Khachigian

2006

Circulation Research

243

205

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Abstract-The immediate-early gene product and zinc finger transcription factor early growth response (Egr)-1 plays a key master regulatory role in multiple cardiovascular pathological processes. This article reviews the amassing recent evidence implicating Egr-1 in atherosclerosis, intimal thickening after acute vascular injury, ischemic pathology, angiogenesis, allograft rejection, and cardiac hypertrophy. Key Words: Egr-1 Ⅲ atherosclerosis Ⅲ vascular injury Ⅲ angiogenesis Ⅲ ischemia and ischemia-reperfusion Ⅲ allograft rejection Ⅲ cardiac hypertrophy E arly growth response (Egr)-1, 1 also known as NGFI-A, 2 zif268, 3 krox-24, 4 and TIS8 5 , is a transcription factor and product of an immediate-early gene located on human chromosome 5q23-q31 encoding 2 exons. 1 The DNA binding domain of Egr-1 contains 3 zinc fingers of the Cys 2 -His 2 subtype that bind preferentially to GC-rich elements. 6 Egr-1 is poorly expressed in the normal artery wall but is activated by acute mechanical injury 7 and other vascular stresses such as angiotensin II, 8 lysophosphatidylcholine, 9 PDGF, 10 FGF-1, 11 FGF-2, 12 and fluid shear stress. 13 Transcription of the Egr-1 gene is dependent on Ras-Raf-MEK-ERK1/2 pathway signaling (which is itself activated by acute vascular injury 8,12,14,15 ) and serum-response elements in the Egr-1 promoter. 16 These elements mediate Egr-1 inducibility in response to a variety of agonists, including thrombin, 17 lipopolysaccharide, 18 and hypoxia, 19 and, as in the c-Fos promoter, involve interactions between ternary complex factors (TCF) and serum response factor (SRF). 20 Recent studies suggest that nuclear accumulation of Egr-1 appears to require interaction of Gab1 (growth factor receptor-bound protein 2 [Grb2]-associated binder-1) with ERK1/2 via the proline-rich METbinding domain in Gab1. 21 Egr-1 is a master regulator because it controls the expression of a wide variety of genes. Oligonucleotide-based microarray analysis provided insights into the spectrum of these Egr-1-dependent genes. Expression of more than 300 genes was altered (229 upregulated, 74 downregulated) 3-fold or more 48 hours following human umbilical vein endothelial cell (HUVEC) infection with an adenovirus-driven form of Egr-1 resistant to transcriptional repression by its endogenous inhibitor NAB. 22 These genes may broadly be grouped as transcription factors (eg, Egr-1, NAB1), signaling factors (eg, Notch3, Rad), growth factors and cytokines (eg, TGF-␤, CLF1), cell-cycle regulators (eg, cyclin D1, p57 kip2 , matrix proteins [eg, fibronectin, osteopontin]) and ion channel regulators (eg, Na ϩ /Ca 2ϩ -exchanger). 22 Egr-1-dependent gene expression involves functional cooperativity (positive and negative) between Egr-1 and a growing number of other transcription or regulatory factors including nuclear factor of activated T cells (NFAT), 23,24 steroidogenic factor-1 (SF-1), 25,26 AP-2 and the glucocorticoid receptor, 27 p300, 25 RelA (p65), 28,29 p53, 30 Sp1 31 as well as NAB (NAB1 32 and NAB2 33 ). It is therefore quite lik...

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Section: Hypoxia and Ischemiamentioning

confidence: 99%

Early Growth Response-1 in Cardiovascular Pathobiology

Khachigian

2006

Circulation Research

243

205

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“…Warm ischaemia following extirpation alters the gene expression profile of a range of tissue types (Miyatake et al, 2004), and changes in gene expression have been seen in colorectal mucosa commencing 20 min after extirpation (Huang et al, 2001). It was hypothesized, therefore, that in addition to the effect of degradation following excision, surgically induced ischaemia occurring during colorectal cancer (CRC) surgery may have a significant impact on gene expression levels, thereby altering the expression profiles of postoperative tumour samples compared with in situ levels.…”

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confidence: 99%

The effect of surgically induced ischaemia on gene expression in a colorectal cancer xenograft model

et al. 2005

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Delays in tissue fixation following tumour vascular clamping and extirpation may adversely affect subsequent protein and mRNA analysis. This study investigated the effect of surgically induced ischaemia in a xenograft model of a colorectal cancer on the expression of a range of prognostic, predictive, and hypoxic markers, with a particular emphasis on thymidylate synthase. Vascular occlusion of human tumour xenografts by D-shaped metal clamps permitted defined periods of tumour ischaemia. Alterations in protein expression were measured by immunohistochemistry and spectral imaging, and changes in mRNA were measured by reverse transcriptase -polymerase chain reaction. Thymidylate synthase expression decreased following vascular occlusion, and this correlated with cyclin A expression. A similar reduction in dihydropyrimidine dehydrogenase was also seen. There were significant changes in the expression of several hypoxic markers, with carbonic anhydrase-9 showing the greatest response. Gene transcriptional levels were also noted to change following tumour clamping. In this xenograft model, surgically induced tumour ischaemia considerably altered the gene expression profiles of several prognostic and hypoxic markers, suggesting that the degree of tumour ischaemia should be minimised prior to tissue fixation.

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“…Warm ischaemia has been shown to alter the gene expression profile of a range of tissue types (Miyatake et al, 2004), and transcriptional changes following extirpation have been demonstrated for multiple genes within a microarray of colorectal mucosal samples beginning 20 min after excision (Huang et al, 2001). Extirpation was not shown to have an affect on DPD enzyme activity in CRC samples (Sadahiro et al, 2003); however, delays in fixation following excision have been shown to impair the analysis of the oestrogen receptor (ER) status in breast cancer patients (Von Wasielewski et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

The impact of surgically induced ischaemia on protein levels in patients undergoing rectal cancer surgery

et al. 2006

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The goal of targeted therapy has driven a search for markers of prognosis and response to adjuvant therapy. The surgical resection of a solid tumour induces tissue ischaemia and acidosis, both potent mediators of gene expression. This study investigated the impact of colorectal cancer (CRC) surgery on prognostic and predictive marker levels. Tumour expression of thymidylate synthase, thymidine phosphorylase, cyclin A, vascular endothelial growth factor (VEGF), carbonic anhydrase-9, hypoxia inducible factor-1a, and glucose transporter-1 (GLUT-1) proteins was determined before and after rectal cancer surgery. Spectral imaging of tissue sections stained by immunohistochemistry provided quantitative data. Surgery altered thymidylate synthase protein expression (P ¼ 0.02), and this correlated with the change in the proliferation marker cyclin A. The expression of hypoxia inducible factor-1a, VEGF, and GLUT-1 proteins was also different following surgery. Colorectal cancer surgery significantly impacts on intratumoral gene expression, suggesting archival specimens may not accurately reflect in situ marker levels. Although rectal cancer was the studied model, the results may be applicable to any solid tumour undergoing extirpation in which molecular markers have been proposed to guide patient therapy.

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Differential modulation of gene expression among rat tissues with warm ischemia

Cited by 32 publications

References 27 publications

Early Growth Response-1 in Cardiovascular Pathobiology

Early Growth Response-1 in Cardiovascular Pathobiology

The effect of surgically induced ischaemia on gene expression in a colorectal cancer xenograft model

The impact of surgically induced ischaemia on protein levels in patients undergoing rectal cancer surgery

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