Identification, expression and protein interaction analysis of Aux/IAA and ARF gene family in Senna tora L / 药学学报

The early response of plant auxin gene family Aux/IAA (auxin/indole-3-acetic acid) and its interaction with auxin response factor (ARF) are important pattern to regulate plant growth and development. This work identified 28 StoIAA and 24 StoARF members based on the whole genome data of the medicinal plant Senna tora L., which were classified into 10 and 8 subfamilies, respectively. Phylogenetic tree and collinearity analysis showed that S. tora has close evolutionary relationship with the IAA and ARF homologous genes of Glycine max, Medicago truncatula, and the segment duplication events dominate the expansion of StoIAA and StoARF. Gene structure analysis showed that the vast majority of StoIAA and StoARF contain characteristic conserved domain. Transcriptome data showed that StoIAAs and StoARFs were expressed in leaves, roots and seeds, some members had tissue specific expression. The StoIAA and StoARF promoter region most contain functional elements related to stress response, growth and development, hormone induction and secondary metabolism. In addition, gene expression analysis showed that many StoIAAs and StoARFs can quickly respond to drought and salt stress and exhibited same expression patterns under both stress condition. The yeast two-hybrid experiment confirmed that StoARF8 and StoARF10 exhibit varying degrees of interaction with multiple StoIAA proteins, respectively. The above results provide a basis for further biological functional analysis of the Aux/IAA and ARF gene family of S. tora.

miRNA-mediated regulation of auxin signaling pathway during plant development and stress responses

Auxin is one of the most important plant growth hormones, playing a crucial role in development as well as instress responses. Auxin biosynthesis and signaling pathway comprises a series of events including auxinperception by the receptor, activation, and function of auxin response factors and control by auxin repressors.All these factors are regulated by several different microRNAs during leaf, flower and fruit development,anther development, nodulation, lateral and adventitious root development, potato tuber development as wellas during heat stress, submergence, boron toxicity, aluminium stress responses, etc., as depicted in the availableliterature. In this review a thorough study on miRNA-mediated regulation of auxin biosynthesis and signalinghas been done in various plant species. The data gathered can be utilized to point out the particular miRNAmediated regulation module which can be utilized to modulate the expression of the miRNA and therebymodulation of the auxin pathway. Information in this review would be beneficial to utilize the miRNAexpression to generate the protocol for engineering plants with altered auxin signaling pathway to obtain betteryield and improved stress tolerance.

Application of an HPLC correction factor method in pharmaceutical analysis / 药学学报

With the in-depth study of related substances and the development of consistency evaluation of generic drugs, relative correction factors are gaining increasing attention. By analyzing the domestic and foreign literature on correction factors in recent years, this paper describes the correction factor component, the current measurement method and its application. The rules and key points of use of an impurity correction factor and its determination and application are described, and some problems in its determination and application are discussed, providing a reference and basis for the standardization of research on impurity correction factors in the future.

The subsequent biological effects of simulated microgravity on endothelial cell growth in HUVECs / 中华创伤杂志(英文版)

<p><b>PURPOSE</b>Microgravity is known to cause endothelium dysfunction in astronauts returning from spaceflight. We aimed to reveal the regulatory mechanism in alterations of human endothelial cells after simulated microgravity (SMG).</p><p><b>METHODS</b>We utilized the rotary cell culture system (RCCS-1) to explore the subsequent effects of SMG on human umbilical vein endothelial cells (HUVECs).</p><p><b>RESULTS</b>SMG-treated HUVECs appeared obvious growth inhibition after return to normal gravity, which might be attributed to a set of responses including alteration of cytoskeleton, decreased cell adhesion capacity and increased apoptosis. Expression levels of mTOR and its downstream Apaf-1 were increased during subsequent culturing after SMG. miR-22 was up-regulated and its target genes SRF and LAMC1 were down-regulated at mRNA levels. LAMC1 siRNAs reduced cell adhesion rate and inhibited stress fiber formation while SRF siRNAs caused apoptosis.</p><p><b>CONCLUSION</b>SMG has the subsequent biological effects on HUVECs, resulting in growth inhibition through mTOR signaling and miR-22-mediated mechanism.</p>

Construction of the full length and N-terminal fragment of serum response factor over-expressing lentiviral plasmid and its impacts on cardiac stem cell differentiation / 临床与实验病理学杂志

Purpose To analyze the effects of full length and N-terminal fragment of serum response factor (SRF-Full and SRF-N) on TGF-β1-induced differentiation in c-Kit + cardiac stem cells (CSC).Methods Rat SRF-Full and SRF-N (1-254 aa) coding sequences were obtained from cDNA library and cloned into the linearized lentviral vector GV358 (Ubi-MCS3FLAG-SV40-EGFP-IRES-puromycin) to generate the recombinant vectors,and then positive clones were selected and sequenced after transducing the competent cells with recombinant vectors.The recombinant lentvirus were packaged through transfecting the HEK293T cells with SRF-Full,SRF-N overexpressing plasmids and viral packaging plasmids.Neonatal SD rat cKit + CSCs were isolated via magnetic activated cell sorting,and TGF-β1-induced differentiation in SRF-Full and SRF-N overexpression virus-infected CSCs was assessed by quantitative PCR.Results SRF-Full and SRF-N coding sequences were successfully obtained and properly cloned into the linearized GV358.The positive clones were selected and further confirmed by sequencing.With the help of packaging plasmids,the SRFFull and SRF-N overexpressing plasmids-transfected HEK293T cells successfully produced the lentiviral particles with the titer of 2 × 108 TU/mL,and the SRF-Full-Flag and SRF-N-Flag fusion protein were detected by Western blot in virus-infected HEK293T cells.Addition of TGF-β1 significantly induced upregulated mRNAs in cardiomyocyte markers (Nkx2.5,Gata4,cTnI) and smooth muscle cell marker (SM22α) but not the epithelia cell marker (vWF) in CSCs.Overexpression of SRF-Full facilitated TGF-β1-triggered cardiomyocyte differentiation.However,SRF-N exerted anti-differentiation effects in TGF-β1-treated cells.Conclusion The SRF-Full and SRF-N overexpressing recombinant lentiviral vectors are successfully constructed.SRF-Full facilitates while SRF-N suppresses TGF-β1-induced cardiomyocyte differentiation in c-Kit + CSCs.

Effects of histamine on mRNA expression of Egr-1 in astrocytes / 中国病理生理杂志

AIM:To explore whether histamine can regulate the expression of early growth response factor-1 (Egr-1) in the cerebral cortex astrocytes.METHODS:Normal wild-type (WT) mice, histidine decarboxylase knockout ( HDC-KO) mice and histamine treated HDC-KO mice were sacrificed for extracting the total RNA of the cerebral cortex. Primary cultured rat cortical astrocytes were treated with histamine at concentrations of 10 -8 , 10 -7 , 10 -6 , 10 -5 or 10 -4 mol/L for 15, 30, 60, 120 or 240 min.H1 or H2 receptor antagonists were pretreated for 15 min before histamine treat-ment.After histamine treatment, the cell total RNA or protein was extracted.The expression of Egr-1 at mRNA and protein levels was determined by real-time PCR and Western blot.RESULTS:The mRNA level of Egr-1 in cerebral cortex of HDC-KO mice was significantly lower than that in WT mice, while exogenous histamine induced the mRNA expression of Egr-1 in HDC-KO mice.In cultured astrocytes, histamine induced the mRNA expression of Egr-1.The maximum increase in the mRNA level of Egr-1 was produced by histamine at concentration of 10 -5 mol/L.In addition, histamine-induced Egr-1 mRNA accumulation peaked at 30 min after commencing stimulation, while histamine significantly increased Egr-1 protein expression at 60 min.Furthermore, histamine-induced Egr-1 expression was inhibited by H1 receptor antagonist but not H2 receptor antagonist.CONCLUSION:Histamine up-regulates the Egr-1 expression in cerebral cortex and cultured astrocytes, which may attribute to H1 receptor activation.

Multi-phenotypic Role of Serum Response Factor in the Gastrointestinal System

Serum response factor (SRF) is a master transcription factor of the actin cytoskeleton that binds to highly conserved CArG boxes located within the majority of smooth muscle cell (SMC)-restricted promoters/enhancers. Although most studies of SRF focus on skeletal muscle, cardiac muscle, and vascular SMCs, SRF research has recently expanded into the gastrointestinal (GI) system. Genome scale analyses of GI SMC transcriptome and CArG boxes (CArGome) have identified new SRF target genes. In addition to circular and longitudinal smooth muscle layers, SRF is also expressed in GI mucosa and cancers. In the GI tract, SRF is the central regulator of genes involved in apoptosis, dedifferentiation, proliferation, and migration of cells. Since SRF is the cell phenotypic modulator, it may play an essential role in the development of myopathy, hypertrophy, ulcers, gastric and colon cancers within the GI tract. Given the multi-functional role displayed by SRF in the digestive system, SRF has received more attention emerging as a potential therapeutic target. This review summarizes the findings in SRF research pertaining to the GI tract and provides valuable insight into future directions.

Expression and clinical significance of serum response factor and vascular endothelial growth factor receptor 2 in gastric carcinoma / 肿瘤研究与临床

Objective To investigate the expression and clinical significance of serum response factor (SRF) and vascular endothelial growth factor receptor (VEGFR2) in gastric carcinoma. Methods SABC immunohistochemical method was used to determine the expressions of SRF and VEGFR2 in 50 cases of gastric carcinoma, 50 cases of surgery incisal edges and 29 cases of lymph node metastasis focus. Results The detection positive rates of SRF and VEGFR2 in gastric carcinoma were 52.00 % (26/50) and 60.00 %(30/50), respectively, which were significantly higher than those in the normal gastric mucosa [16.00 % (8/50) and 10.00 % (5/50), respectively] (P0.05), but closely correlated to differentiation degree, invasion depth and lymph node metastasis (P<0.05). The expressions of SRF and VEGFR2 in the gastric carcinoma were positively correlated (r= 0.594, P< 0.05). Conclusion Overexpressions of SRF and VEGFR2 in gastric carcinoma can be regarded as the poorly prognostic markers and play an important role in invasion and metastasis of gastric carcinoma.

The effect of Y-27632 on invasion and migration of gastric carcinoma cell line SGC-7901 / 基础医学与临床

Objective_To study the effect of Y-27632 on invasion and motility of SGC-7901 gastric carcinoma cells, and to find whether Y-27632 excerts the effect by attenuating SRF expression.Methods_SGC-7901 gastric carcinoma cells were divided into 3 groups:1)blank control group;2)Y-27632 group;3)siRNA-SRF-1107 group. Transfected siRNA-SRF or incubated by Y-27632 48 h.The effect of Y-27632 on proliferation suppressions of SGC-7901 gastric carcinoma cells was detected by CCK-8 assay.Cell invasion was examined by Transwell and wound healing test.The expression of SRF, ROCK1, E-cadherin, β-catenin, F-actin, MRTF-A and Cyclin D1 were detected by Western blot.Results_Y-27632 inhibited invasion (P<0.05)but had no effect on proliferation of SGC-7901 gastric carcinoma cells.Y-27632 reduced ROCK1, MRTF-A, F-actin, SRF protein expressions by 37.0%, 44.3%, 62.7%and 62.7%respectively, and E-cadherin protein expression was up-regulated by 2.64 folds(P<0.05).Conclusions_The inhibition of ROCK and up-regulation of E-cadherin by Y-27632 can inhibit the invasion and migration of SGC-7901 gastric carcinoma cells that is explained at least, in part, by attenuating SRF expression.

Effect of glycyrrhizin on serum levels of PDGF, IL-17, MCP-1 and SRF in patients with glioma / 中国生化药物杂志

Objective To analyse effect of glycyrrhizin on serum levels of platelet derived growth factor ( PDGF ) , interleukin 17 ( IL-17 ) , monocyte chemotactic protein 1 (MCP-1) and serum response factor (SRF) in patients with glioma.Methods 48 patients who were diagnosed with glioma in our hospital were collected.All patients were randomly divided into experimental group and control group,24 cases in each group.All patients were treated with surgery,control group was treated with temozolomid capsule(150 mg/m2 ) orally, one times per day, 28 days for a treatment period of 5 days continuous administration.On the basis of control group, experimental group was treated with compound ammonium glycyrrhetate injection 40 mL, dissolved in 250 mL 5% glucose solution intravenously,one times per day,four weeks was a period of treatment.After two groups were treated two period of treatment,the serum levels of PDGF, IL-17,MCP-1and SRF were detected in all patients.Results After treatment, compared with control group, the serum PDGF level was lower than that of experimental group (P<0.05);the serum IL-17 level was lower than that of experimental group (P<0.05);the serum MCP-1 level was higher than that of experimental group ( P <0.05 );the serum SRF level was lower than that of experimental group ( P <0.05).Conclusion Glycyrrhizin could significantly reduce the serum PDGF, IL-17 and SRF levels,increase MCP-1 levels, have guidance significance for clinic.

Change of serum response factor expression in eyelid of different embryo development stages of B6-Co mice / 中华实验眼科杂志

Background Mutant C57BL/6 mouse with corneal opacity (B6-Co) appears eye open at birth (EOB) phenotype,which is a good animal model in the study of developmental mechanism of eyelid.Investigating the relationship between serum response factor (SRF) and EOB phenotype can provide theoretical support for the research on the mechanism of innate defects in eyelid development in humans.Objective This study was to assess the dynamic expressions of SRF in eyelid of embryonic B6-Co mouse.Methods Total RNA was extracted from B6 and B6-Co mice eyelid tissue at embryonic day 16.5 (E16.5 d),E17.5 d and E18.5 d.The relative expression levels of SRF mRNA and protein in the eyelid tissue of B6 and B6-Co embryonic mice were assayed by real-time quantitative PCR and Western blot,respectively.In situ expressions of SRF protein in eyelid of B6-Co mice and B6 mice were detected using immunofluorescence technique.The use and care of the animals complied with the Regulation for the Administration of Affair Concerning Experimental Animals of Nantong University.Results The relative expression levels ofSRF mRNA in the eyelids were 0.41±0.06 and 0.24±0.17 in E16.5 d and E17.5 d of B6-Co mice,showing a significant decline in comparison with 1.03 ±0.17 and 1.01 ±0.09 in the B6 mice (P =0.025,0.017).The expression levels of SRF protein in the eyelids of E16.5 d and E17.5 d B6-Co mice were 0.08±0.01 and 0.08± 0.01,which were significantly lower than 0.12 ±0.03 and 0.13 ± 0.02 of B6 mice (P =0.036,0.024).However,there were no significant differences in the expression levels of SRF mRNA and protein in E18.5 d between the B6-Co mice and B6 mice (P =0.387,0.774).Immunofluorescence assay displayed that SRF was expressed in the keratinocytes of eyelids in both mice,but the fluorescence intensity was weaker in the B6-Co mice.Conclusions SRF probably interrupts the developing process of eyelid in early embryo of B6-Co mice.

Serum Response Factor Is Essential for Prenatal Gastrointestinal Smooth Muscle Development and Maintenance of Differentiated Phenotype

BACKGROUND/AIMS: Smooth muscle cells (SMCs) characteristically express serum response factor (SRF), which regulates their development. The role of SRF in SMC plasticity in the pathophysiological conditions of gastrointestinal (GI) tract is less characterized. METHODS: We generated SMC-specific Srf knockout mice and characterized the prenatally lethal phenotype using ultrasound biomicroscopy and histological analysis. We used small bowel partial obstruction surgeries and primary cell culture using cell-specific enhanced green fluorescent protein (EGFP) mouse lines to study phenotypic and molecular changes of SMCs by immunofluorescence, Western blotting, and quantitative polymerase chain reaction. Finally we examined SRF change in human rectal prolapse tissue by immunofluorescence. RESULTS: Congenital SMC-specific Srf knockout mice died before birth and displayed severe GI and cardiac defects. Partial obstruction resulted in an overall increase in SRF protein expression. However, individual SMCs appeared to gradually lose SRF in the hypertrophic muscle. Cells expressing low levels of SRF also expressed low levels of platelet-derived growth factor receptor alpha (PDGFRalphalow) and Ki67. SMCs grown in culture recaptured the phenotypic switch from differentiated SMCs to proliferative PDGFRalphalow cells. The immediate and dramatic reduction of Srf and Myh11 mRNA expression confirmed the phenotypic change. Human rectal prolapse tissue also demonstrated significant loss of SRF expression. CONCLUSIONS: SRF expression in SMCs is essential for prenatal development of the GI tract and heart. Following partial obstruction, SMCs down-regulate SRF to transition into proliferative PDGFRalphalow cells that may represent a phenotype responsible for their plasticity. These findings demonstrate that SRF also plays a critical role in the remodeling process following GI injury.

SRF expression and its biological significance in gastric carcinoma cells / 中国肿瘤临床

Objective:This study aims to explore the relationship between serum response factor (SRF) expression level and gas-tric cancer progression by detecting SRF expression level in cancer cells. Methods:The SRF gene in SGC-7901 cells was silenced by RNA interference. Transfection efficiency was detected by fluorescence microscopy, cell proliferation by CCK 8 method, SRF gene and protein expression level by real-time polymerase chain reaction and Western blot, and cell cycle by flow cytometry. Results:Cell treat-ment with siRNA-SRF induced significant reduction in SRF mRNA levels. Western blot analysis showed that SRF protein decreased by 40.1%in the siRNA group compared with that in the control group (P<0.05). Compared with the blank, negative, and mock transfection control groups, cell proliferation of the siRNA-SRF group decreased. The inhibition ratio reached 64.24%, as measured by the CCK-8 assay (P<0.05). Treatment with siRNA could block SGC-7901 cell cycle at G0/G1 phase (P<0.05). Conclusion:SRF expression is close-ly associated with gastric carcinoma cell proliferation. SRF protein level detection can provide a certain reference value in evaluating malignant gastric carcinoma progression. SRF is possibly an important target for the prevention and control of gastric cancers.

Early Growth Response 1— A Transcription Factor in the crossfire of Signal Transduction Cascades.

Early growth response-1 (Egr-1) is a Cys2-His2-type zinc-finger transcription factor. A broad range of extracellular stimuli is capable of activating Egr-1, thus mediating growth, proliferation, differentiation or apoptosis. Egr-1 is, therefore, participating in the progression of a variety of diseases such as atherosclerosis or cancer. Functional response elements connect Egr-1 to signal transduction cascades targeting Egr-1. Five serum response elements (SRE) have been identified in the promoter region of Egr-1, the binding region of serum response factor (SRF). The Rho/Rho-kinase pathway has been shown to regulate actin reorganization via LIM-kinase mediated cofilin phosphorylation. Recent studies have revealed that the actin binding striated muscle activator of Rho signaling (STARS) promotes translocation of myosin related transcription factors (MRTFs) into the nucleus, leading to SRF activation. The ternary complex factor (TCF) Elk-1 eventually bridges the gap between SRF-mediated gene transcription and the Raf/MEK/ERK pathway. Moreover, the Egr-1 promoter owns two cAMP response elements (CREs), whose relevance for gene expression is still unclear. An Egr-1 binding site (EBS) located on the Egr-1 promoter itself is arguing for a negative feedback mechanism. The acquired knowledge on transcriptional regulation of Egr-1 is not entirely understood. In this review, we highlight upstream and downstream signaling in vitro and in vivo associated with Egr-1.

Essential regulatory elements for NHE3 gene transcription in renal proximal tubule cells

The objectives of the present study were to identify the cis-elements of the promoter absolutely required for the efficient rat NHE3 gene transcription and to locate positive and negative regulatory elements in the 5’-flanking sequence (5’FS), which might modulate the gene expression in proximal tubules, and to compare this result to those reported for intestinal cell lines. We analyzed the promoter activity of different 5’FS segments of the rat NHE3 gene, in the OKP renal proximal tubule cell line by measuring the activity of the reporter gene luciferase. Because the segment spanning the first 157 bp of 5’FS was the most active it was studied in more detail by sequential deletions, point mutations, and gel shift assays. The essential elements for gene transcription are in the region -85 to -33, where we can identify consensual binding sites for Sp1 and EGR-1, which are relevant to NHE3 gene basal transcription. Although a low level of transcription is still possible when the first 25 bp of the 5’FS are used as promoter, efficient transcription only occurs with 44 bp of 5’FS. There are negative regulatory elements in the segments spanning -1196 to -889 and -467 to -152, and positive enhancers between -889 and -479 bp of 5’FS. Transcription factors in the OKP cell nuclear extract efficiently bound to DNA elements of rat NHE3 promoter as demonstrated by gel shift assays, suggesting a high level of similarity between transcription factors of both species, including Sp1 and EGR-1.

Effects of hypoxic preconditioning on EGR-1 expression of hepatocytes in a rat model undergoing liver autotransplantation / 中华普通外科杂志

Objective To investigate the effect of hypoxic preconditioning on hepatocytes early growth response factor 1 ( EGR-1 ) in a rat liver autotransplantation. Methods The rat portal vein perfusion model was established for donor liver autotransplantation. Rats were then divided into group A:hypoxic preconditioning was done before transplantation; group B: rats undergoing liver transplantation without preconditioning; group C: Normal control group of rats. Liver histopathological changes, the mRNA expression of HIF-1, TNF-1 and the WB results of EGR-1 were compared between groups. Results The expression of HIF-1 α RNA determined in group A was more obvious than in group B and group C. Six hours after surgery, the expression in group A was significantly higher than that in group B (t =9. 601, df= 10, 2-tailed Sig = 0. 000, P<0. 05 ) ; Egr-1 protein expression in group A and group B increased after surgery,with that in group A being significantly lower than that in group B. The RT-PCR expression of TNF-α RNA in group B compared with group A and group C was more obvious. Six hours after operation, the expression of TNF in group B was significantly higher than that in group A ( t = -12. 067, df = 10, 2-tailed Sig =0. 000, P<0. 05 ). The expression of Egr-1 was positively correlated with that of TNF. A liver cell pathology showed less severe injury in structure of hepatic lobule, mild swelling of liver cells, no significant changes in liver tissue. Conclusions Hypoxic preconditioning adaptation in rat liver transplantation generates modest increase in EGR-1, and reduces the production of TNF and other inflammatory factors.

Expression and Prognostic Significance of Serum Response Factor in Cholangiocarcinoma

BACKGROUND: Serum response factor (SRF) is a transcriptional factor that plays an important role in cell growth and differentiation for several types of cells. The expression of SRF in cholangiocarcinoma (CC) and its potential role has not been examined. The aim of this study was to determine the relationship between the expression of SRF in CC and the clinicopathological parameters, as well as patient survival. METHODS: We analyzed the expression of SRF in 84 surgically resected cases of CC (33 cases of intrahepatic CC [ICC] and 51 cases of extrahepatic CC [ECC]) by using immunohistochemistry. RESULTS: The positive expression of SRF was detected in 48.8% of the cases of CC (42.4% in ICC, 52.9% in ECC). SRF was predominantly expressed in the CC cells with intense labeling in the nucleus. A SRF expression was significantly associated with the cell proliferation rate (Ki-67 labeling index, p=0.046) and poor patient survival (p=0.002). The tumor differentiation (p=0.038), the T category (p<0.001), lymph node and distant metastasis (p<0.001, p=0.009) and nerve and vessel invasion (p=0.010, p=0.012) were also found to be significantly associated with a poor CC prognosis. CONCLUSIONS: These results suggest that the SRF may play a role in the tumor cell proliferation of CC, and its expression in tumor cells can provide additional prognostic information.

Serum response factor play a regulative role in the gene expression in heart failure / 老年心脏病学杂志（英文版）

To investigate the relationship between transcription factor and the change of protein expression levels in heart failure. Methods Bioinformatic method was used to analyze the data of binding-sites on the 5 ' flaking regions of four genes whose mRNA level changed in failing heart from three databases about nucleic acid-EMBL, transcriptional regulation factor-TRANSFAC and protein-SWISS-PORT.The expression level of selected transcription factor was determined by immunohischemical method.Results Nine transcription factors were inferred to influence the proteins' levels in occurrence and development of heart failure.Serum response factor (SRF) was selected from the nine factors and assayed. The results showed that there was a higher level of SRF in healthy group than in chronic heart failure (CHF), and the level was associated with the degree of CHF. It was also found that there was a relative higher level of SRF in the acute myocardial infarction (AMI) than that in CHF, but which was lower than the healthy. Conclusion It showed that SRF had a quantitative change in the development of heart failure, and suggested SRF might play an important regulative role in heart failure. The expression changes of proteins related to myocardial function might be regulated by the quantitative change of transcription factor(s).

Reduction of inflammatory-related factor expression in experimental acute pancreatitis in Egr-1 knockout mice / 中国病理生理杂志

AIM: To observe the effects of Egr-1 gene knockout on the expression of inflammatory-related factors in pancreatic tissue in a mouse acute pancreatitis model.METHODS: The experimental pancreatitis was induced by high-dose of cearulein in wildtype mice and Egr-1 knockout mice.The pancreatitis indexes,such as serum amylase,pancreata edema,and myeloperoxidase(MPO) levels in pancreata and lungs were recorded.The mRNA levels of tissue factor(TF),plasminogen activator inhibitor(PAI-1),monocyte chemoattractant protein(MCP-1),Gro-1,IL-6 and ICAM-1 were measured by quantitative PCR.RESULTS: Contrary to wildtype mice,typical pancreatitis was not induced by high-dose cearulein in the Egr-1 knockout mice,not only markedly reduced edema in pancreata and lungs,but decreased MPO levels in lungs as well were found.Furthermore,the mRNA of TF,PAI,MCAP,ICAM-1 and IL-6 in pancreata were significantly decreased in Egr-1 knockout mice.CONCLUSION: The severity of pancreatitis and lung damage is ameliorated in Egr-1 knockout mice stimulated by high-dosage of cearulein,which was probably mediated by decreasing expression of inflammatory-related factors in pancreata,such as TF,PAI,MCP-1,ICAM-1 and IL-6.