Novel expression of vascular endothelial growth factor isoforms in the pancreas and pancreatic cystic lesions.

Novel expression of vascular endothelial growth factor isoforms in the pancreas and pancreatic cystic lesions.
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血管内皮生长因子同工型在胰腺和胰腺囊性病变中的新表达。

DOI:
10.1016/j.biochi.2020.12.016
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发表时间:
2021-03
期刊:
影响因子:
3.9
通讯作者:
Schmidt CM
Schmidt CM
中科院分区:
生物学3区
文献类型:
--
作者:
Yip-Schneider MT;Wu H;Schmidt CM

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血管内皮生长因子(VEGF)-A在血管生成和血管通透性中起着重要的生物学作用。我们之前确定VEGF-A是良性胰腺囊性病变(浆液性囊性肿瘤)的准确生物标志物。在本研究中,我们试图进一步表征VEGF-A及其剪接异构体在包括SCN在内的不同胰腺囊肿中的表达。接受手术的患者同意收集胰腺囊性病变组织(SCN、假性囊肿、粘液囊肿)和正常邻近胰腺以及胰腺囊肿液。从组织中分离RNA后,采用real-time PCR (qPCR)定量分析VEGF-A基因的相对表达,并采用逆转录酶(RT)-PCR评估VEGF-A异构体的表达。VEGF-A基因的相对表达在SCN中显著升高,表明与其他胰腺囊肿组织相比,SCN中的转录上调(P<0.0001)。在正常邻近胰腺和胰腺囊性病变中均检测到VEGF-189、- 165、145和- 121剪接变异体;新的VEGF-111异构体在正常组织和囊肿组织中表达不同。最后,用特异的elisa检测胰腺囊肿液中VEGF同型异构体水平。胰腺囊肿液中存在VEGF-165、- 145和- 121蛋白;SCN囊肿液中VEGF-165水平明显升高。因此,多种VEGF亚型在正常胰腺和胰腺囊肿中表达。特别令人感兴趣的是VEGF-145和- 111,它们以前没有在人类胰腺中被描述过,它们可能在健康和/或疾病中表现出独特的生物活性。
Vascular endothelial growth factor (VEGF)-A is known to play key biological roles in angiogenesis and vascular permeability. We previously identified VEGF-A as an accurate biomarker of benign pancreatic cystic lesions known as serous cystic neoplasms (SCN). In the present study, we seek to further characterize the expression of VEGF-A and its splice isoforms in different pancreatic cysts including SCN. Patients undergoing surgery were consented for the collection of pancreatic cystic lesion tissue (SCN, pseudocysts, mucinous cysts) and normal adjacent pancreas as well as pancreatic cyst fluid. Following RNA isolation from the tissues, relative VEGF-A gene expression was quantitatively analyzed using real-time PCR (qPCR), and VEGF-A isoform expression was evaluated by reverse transcriptase (RT)-PCR. Relative VEGF-A gene expression was significantly increased in SCN, demonstrating transcriptional upregulation in SCN compared to other pancreatic cyst tissues (P<0.0001). VEGF-189, −165, 145, and −121 splice variants were detected in both normal adjacent pancreas and pancreatic cystic lesions; the novel VEGF-111 isoform was variably expressed in normal and cyst tissues. Finally, VEGF isoform levels in pancreatic cyst fluid were measured by isoform-specific ELISAs. VEGF-165, −145, and −121 proteins were present in pancreatic cyst fluids; VEGF-165 levels were significantly higher in SCN cyst fluid. Thus, multiple VEGF isoforms were expressed in normal pancreas and pancreatic cysts. Of particular interest are VEGF-145 and - 111, which have not previously been described in human pancreas where they may exhibit unique biological activities in health and/or disease.
一种多模式测试,可指导胰腺囊肿患者的管理。
DOI: 10.1126/scitranslmed.aav4772
发表时间: 2019-07-17
影响因子: 17.1
作者:
Springer S;Masica DL;Dal Molin M;Douville C;Thoburn CJ;Afsari B;Li L;Cohen JD;Thompson E;Allen PJ;Klimstra DS;Schattner MA;Schmidt CM;Yip-Schneider M;Simpson RE;Fernandez-Del Castillo C;Mino-Kenudson M;Brugge W;Brand RE;Singhi AD;Scarpa A;Lawlor R;Salvia R;Zamboni G;Hong SM;Hwang DW;Jang JY;Kwon W;Swan N;Geoghegan J;Falconi M;Crippa S;Doglioni C;Paulino J;Schulick RD;Edil BH;Park W;Yachida S;Hijioka S;van Hooft J;He J;Weiss MJ;Burkhart R;Makary M;Canto MI;Goggins MG;Ptak J;Dobbyn L;Schaefer J;Sillman N;Popoli M;Klein AP;Tomasetti C;Karchin R;Papadopoulos N;Kinzler KW;Vogelstein B;Wolfgang CL;Hruban RH;Lennon AM
通讯作者: Lennon AM
DOI: 10.1159/000178890
发表时间: 2009-01-01
期刊: PANCREATOLOGY
影响因子: 3.6
作者:
Thirabanjasak, Duangpen;Basturk, Olca;Adsay, N. Volkan
通讯作者: Adsay, N. Volkan
DOI: 10.1093/molehr/7.1.57
发表时间: 2001-01-01
影响因子: 4
作者:
Krüssell, JS;Behr, B;Polan, ML
通讯作者: Polan, ML
DOI: 10.1016/s0002-9440(10)64799-2
发表时间: 2000-11-01
影响因子: 6
作者:
Mohr, VH;Vortmeyer, AO;Lubensky, IA
通讯作者: Lubensky, IA
DOI: 10.1016/j.jamcollsurg.2017.05.003
发表时间: 2017-07-01
影响因子: 5.2
作者:
Carr, Rosalie A.;Yip-Schneider, Michele T.;Schmidt, C. Max
通讯作者: Schmidt, C. Max