Zhou Hui,Li Suolin,Shi Baojun,et al.Hepatic expression of PDGF-BB in infants with biliary atresia and its correlation with epithelial mesenchymal transition[J].Journal of Clinical Pediatric Surgery,2023,22(03):238-243.[doi:10.3760/cma.j.cn101785-202012064-007]
PDGF-BB在胆道闭锁患儿肝脏中的表达及其与上皮间质转化的相关性研究
- Title:
- Hepatic expression of PDGF-BB in infants with biliary atresia and its correlation with epithelial mesenchymal transition
- Keywords:
- Biliary Atresia; Platelet-Derived Growth Factor; Epithelial-Mesenchymal Transition; Protein Biosynthesis
- 摘要:
- 目的 探讨胆道闭锁(biliary atresia,BA)患儿肝脏中血小板源性生长因子-BB(platelet-derived growth factor,PDGF-BB)、锌指转录因子(Snail 1)和上皮间质转化(epithelial-mesenchymal transition,EMT)的表达情况以及三者之间的关系。方法 回顾性分析2018年1月至2019年12月河北医科大学第二医院小儿外科收治的BA患儿25例(BA组)、胆总管囊肿患儿15例(CCC组)以及肝脏肿瘤患儿10例(NL组)的临床资料;收集患儿活检组织,分别应用免疫组织化学法、实时荧光定量PCR检测PDGF-BB、Snail 1、E钙黏素(E-cadherin)和N钙黏素(N-cadherin)的表达情况,并对上述指标进行相关性分析。结果 BA组患儿肝脏中PDGF-BB、Snail 1和N-cadherin的mRNA和蛋白表达均显著高于CCC组和NL组,差异有统计学意义(P＜0.05),E-cadherin的mRNA和蛋白表达均显著低于CCC组和NL组,差异有统计学意义(P＜0.05)。其中PDGF-BB与Snail 1 mRNA和蛋白的表达呈正相关(r=0.772,P<0.05;r=0.780,P<0.05);PDGF-BB与N-cadherin mRNA和蛋白表达呈正相关性(r=0.835,P<0.05;r=0.702,P<0.05);PDGF-BB与E-cadherin mRNA和蛋白表达呈负相关(r=-0.756,P<0.05;r=-0.696,P<0.05);Snail 1与N-cadherin mRNA和蛋白表达呈正相关(r=0.723,P<0.05;r=0.702,P<0.05);Snail 1与E-cadherin mRNA和蛋白表达呈负相关(r=-0.720,P<0.05;r=-0.636,P<0.05)。肝纤维化程度与PDGF-BB的表达呈正相关(r=0.977,P<0.05);肝纤维化程度与E-cadherin蛋白表达呈负相关(r=-0.722,P<0.05);肝纤维化程度与N-cadherin蛋白表达呈正相关(r=0.711,P<0.05);肝纤维化程度与Snail 1表达呈正相关(r=-0.810,P<0.05)。结论 PDGF-BB可能通过增强转录因子Snail 1的转录活性,促进BA患儿发生EMT,这为BA患儿的诊治提供了新的理论依据。
- Abstract:
- Objective To explore the hepatic expression of platelet-derived growth factor-BB (PDGF-BB),Snail 1 and epithelial-mesenchymal transition (EMT) in children of biliary atresia (BA) and examine the relationship among three parameters.Methods From January 2018 to December 2019,there were BA (n=25),choledochal cysts (CCC,n=15) and liver tumors (NL,n=10).After collecting biopsy tissues,immunohistochemistry and real-time fluorescent quantitative polymerase chain reaction (PCR) were employed for detecting the expression of PDGF-BB,Snail 1,E-cadherin and N-cadherin and analyzing their correlations.Results mRNA and protein expressions of PDGF-BB,Snail 1 and N-cadherin were significantly higher in liver of BA group than those of CCC/NL group (P<0.05); mRNA and protein expressions of E-cadherin were significantly lower than that of CCC/NL group (P<0.05).PDGF-BB was correlated positively with Snail 1 mRNA and protein expressions (r=0.772,P<0.05; r=0.780,P<0.05); PDGF-BB was correlated positively with N-cadherin mRNA and protein expressions (r=0.835,P<0.05; r=0.702,P<0.05); PDGF-BB and E-cadherin mRNA and protein expressions were correlated negatively (r=-0.756,P<0.05; r=-0.696,P<0.05); Snail 1 and N-cadherin mRNA and protein expression were correlated positively (r=0.723,P<0.05; r=0.702,P<0.05); Snail 1 was correlated negatively with E-cadherin mRNA and protein expressions (r=-0.720,P<0.05; r=-0.636,P<0.05).Conclusion In BA children,PDGF-BB may promote EMT through enhancing the transcription activity of transcription factor Snail 1.Thus it may provide new theoretical rationales for diagnosing and treating BA children.
参考文献/References:
[1] Safwan M,Ramachandran P,Vij M,et al.Impact of ductal plate malformation on survival with native liver in children with biliary atresia[J].Pediatr Surg Int,2015,31(9):837-843.DOI:10.1007/s00383-015-3728-6.
[2] Thiery JP,Acloque H,Huang RY,et al.Epithelial-mesenchymal transitions in development and disease[J].Cell,2009,139(5):871-890.DOI:10.1016/j.cell.2009.11.007.
[3] 孙雪,任红霞.胆道闭锁发生与肝纤维化的分子机制研究进展[J].临床小儿外科杂志,2019,18(5):432-436.DOI:10.3969/j.issn.1671-6353.2019.05.019. Sun X,Ren HX.Research advances in molecular mechanisms of biliary atresia and hepatic fibrosis[J].J Clin Ped Sur,2019,18(5):432-436.DOI:10.3969/j.issn.1671-6353.2019.05.019.
[4] Zhang CY,Yuan WG,He P,et al.Liver fibrosis and hepatic stellate cells:Etiology,pathological hallmarks and therapeutic targets[J].World J Gastroenterol,2016,22(48):10512-10522.DOI:10.3748/wjg.v22.i48.10512.
[5] Ying HZ,Chen Q,Zhang WY,et al.PDGF signaling pathway in hepatic fibrosis pathogenesis and therapeutics (Review)[J].Mol Med Rep,2017,16(6):7879-7889.DOI:10.3892/mmr.2017.7641.
[6] Weiskirchen R,Weiskirchen S,Tacke F.Organ and tissue fibrosis:molecular signals,cellular mechanisms and translational implications[J].Mol Aspects Med,2019,65:2-15.DOI:10.1016/j.mam.2018.06.003.
[7] Jain MK,Adams-Huet B,Terekhova D,et al.Acute and chronic immune biomarker changes during interferon/ribavirin treatment in HIV/HCV co-infected patients[J].J Viral Hepat,2015,22(1):25-36.DOI:10.1111/jvh.12226.
[8] Wu X,Liu GZ,Mu M,et al.Augmenter of liver regeneration gene therapy using a novel minicircle DNA vector alleviates liver fibrosis in rats[J].Hum Gene Ther,2016,27(11):880-891.DOI:10.1089/hum.2016.006.
[9] Shah R,Reyes-Gordillo K,Rojkind M.Thymosin β4 inhibits PDGF-BB induced activation,proliferation,and migration of human hepatic stellate cells via its actin-binding domain[J].Expert Opin Biol Ther,2018,18(sup1):177-184.DOI:10.1080/14712598.2018.1478961.
[10] Maturi V,Morén A,Enroth S,et al.Genomewide binding of transcription factor Snail1 in triple-negative breast cancer cells[J].Mol Oncol,2018,12(7):1153-1174.DOI:10.1002/1878-0261.12317.
[11] Cheng JC,Auersperg N,Leung PCK.TGF-beta induces serous bo-rderline ovarian tumor cell invasion by activating EMT but triggers apoptosis in low-grade serous ovarian carcinoma cells[J].PLoS One,2012,7(8):e42436.DOI:10.1371/journal.pone.0042436.
[12] Díaz R,Kim JW,Hui JJ,et al.Evidence for the epithelial to mesenchymal transition in biliary atresia fibrosis[J].Hum Pathol,2008,39(1):102-115.DOI:10.1016/j.humpath.2007.05.021.
[13] Canesin G,Cuevas EP,Santos V,et al.Lysyl oxidase-like 2(LO-XL2) and E47 EMT factor:novel partners in E-cadherin repression and early metastasis colonization[J].Oncogene,2015,34(8):951-964.DOI:10.1038/onc.2014.23.
[14] Xie GH,Diehl AM.Evidence for and against epithelial-to-mesenchymal transition in the liver[J].Am J Physiol Gastrointest Liver Physiol,2013,305(12):G881-G900.DOI:10.1152/ajpgi.00289.2013.
[15] Doble BW,Woodgett JR.Role of glycogen synthase kinase-3 in cell fate and epithelial-mesenchymal transitions[J].Cells Tissues Organs,2007,185(1/3):73-84.DOI:10.1159/000101306.
[16] Syn WK,Choi SS,Liaskou E,et al.Osteopontin is induced by hedgehog pathway activation and promotes fibrosis progression in nonalcoholic steatohepatitis[J].Hepatology,2011,53(1):106-115.DOI:10.1002/hep.23998.
[17] 彭龙希,高思楠,王媛,等.青蒿琥酯在大鼠体内外抗肝纤维化的作用[J].中国药理学通报,2016,32(5):658-663.DOI:10.3969/j.issn.1001-1978.2016.05.013. Peng LX,Gao SN,Wang Y,et al.Effect of artesunate on rat liver fibrogenesis in vitro and in vivo[J].Chin Pharmacol Bull,2016,32(5):658-663.DOI:10.3969/j.issn.1001-1978.2016.05.013.
[18] Chang KK,Yoon C,Yi BC,et al.Platelet-derived growth factor receptor-α and-β promote cancer stem cell phenotypes in sarcomas[J].Oncogenesis,2018,7(6):47.DOI:10.1038/s41389-018-0059-1.
相似文献/References:
[1]毛永忠,汤绍涛,阮庆兰,等.胆道闭锁肝组织MMP-1、MMP-2、TIMP-1的表达与预后研究[J].临床小儿外科杂志,2007,6(01):5.
[2]毛永忠,汤绍涛,阮庆兰,等.胆道闭锁肝脏组织MMP-2、TGF-β_1的表达及意义[J].临床小儿外科杂志,2007,6(03):5.
[3]余梦楠 刘钢 黄柳明 王伟. 胆道闭锁术后反复发作性胆管炎的细菌谱分析及抗生素选择[J].临床小儿外科杂志,2012,11(03):187.
[J].Journal of Clinical Pediatric Surgery,2012,11(03):187.
[4]董淳强 杨体泉 董昆. 胆道闭锁术后早期胆管炎风险因素分析[J].临床小儿外科杂志,2013,12(05):348.
[5]陈功 郑珊 孙松. 不同年龄胆道闭锁患儿手术效果分析[J].临床小儿外科杂志,2014,13(01):22.
[6]谭梅军 陶强 黄金狮. IL-17在胆道闭锁患儿肝组织中的表达及意义[J].临床小儿外科杂志,2014,13(04):302.
[7]杨文萍 吴艳 张守华. 胆道闭锁患者肝脏组织病理改变的综合评价[J].临床小儿外科杂志,2015,14(01):10.
[8]李康 阳历 汤绍涛. 胆道闭锁患者肝内胆管γδT 细胞和调节性T细胞浸润及意义[J].临床小儿外科杂志,2015,14(01):16.
[9]刘丹丹 詹江华 高伟. 胆道闭锁患者肝门的病理解剖学研究[J].临床小儿外科杂志,2015,14(01):20.
[10]张震 李龙 乔国梁. 胆道闭锁Kasai术后生存率及条件生存率分析[J].临床小儿外科杂志,2015,14(01):25.
备注/Memo
收稿日期:2020-12-30。
基金项目:河北省政府资助临床医学优秀人才培养计划项目(2019008)
通讯作者:李索林,Email:lisuolin@263.net