钙黏蛋白-11在胆道闭锁患儿肝组织中的表达及意义
收稿日期: 2021-07-14
网络出版日期: 2022-02-11
基金资助
国家自然科学基金(81770517)
Expression and significance of cadherin-11 in liver of children with biliary atresia
Received date: 2021-07-14
Online published: 2022-02-11
目的 分析钙黏蛋白-11(cadherin-11,CDH11)在胆道闭锁(biliary atresia,BA)患儿肝组织内的表达及意义。方法 选取2014年11月至2016年12月就诊的BA和胆总管囊肿(CC)患儿作为研究对象。分析患儿肝脏CDH11与肝纤维化标志基因和血清肝功能指标的相关性。结果 BA组50例,女25例、男25例,中位年龄59.5(46.8~71.8)天;CC组8例,女5例、男3例,中位年龄70.0(49.0~125.3)天。BA组患儿肝脏中CDH11 mRNA表达水平显著高于CC组,差异有统计学意义(P<0.01)。BA肝内CDH11 mRNA表达水平与转化生长因子β1(TGFB1)、转化生长因子β2(TGFB2)、角蛋白19(KRT19)、肌动蛋白α2(ACTA2)、Ⅰ型胶原α1链(COL1A1)和Ⅳ型胶原α1链(COL4A1) mRNA表达水平呈显著正相关(r= 0.36~0.73,P均<0.01)。与轻度肝纤维化BA患儿相比,CDH11表达水平在重度肝纤维化BA患儿肝内显著升高(P<0.01)。BA肝内CDH11 mRNA表达水平与血清γ-谷氨酰转肽酶(γ-GT)、总胆红素(TBil)、直接胆红素(DBil)和胆汁酸(TBA)水平呈正相关(r=0.26~0.37,P均<0.05)。结论 与CC患儿相比,CDH11在BA患儿肝组织中表达水平显著升高。BA肝内CDH11表达水平与肝纤维化进程和肝脏损伤程度密切相关。
吴博 , 田心蓓 , 卢颖 , 杜君 , 肖永陶 . 钙黏蛋白-11在胆道闭锁患儿肝组织中的表达及意义[J]. 临床儿科杂志, 2022 , 40(2) : 134 -138 . DOI: 10.12372/jcp.2022.21e1058
Objective To analyze the expression and significance of cadherin-11 (CDH11) in livers of children with biliary atresia (BA). Methods Fifty children with BA and eight children with choledochal cyst (CC) were selected as the research objects. The expression levels of CDH11 and liver fibrotic marker genes in the livers of the children were evaluated by quantitative real-time polymerase chain reaction. The correlation between CDH11 and liver fibrotic marker genes or serum liver function markers was analyzed. Results The mRNA levels of CDH11 were significantly elevated in livers of children with BA compared to children with CC (P< 0.01). Hepatic CDH11 mRNA levels were positively correlated with the expression levels of transforming growth factor beta 1, transforming growth factor beta 2, keratin 19, actin alpha 2, smooth muscle, collagen type I alpha 1 and collagen type IV alpha 1 in children with BA (r= 0.36 ~ 0.73, all P< 0.01). The mRNA levels of CDH11 in livers of BA patients with severe liver fibrosis significantly increased compared to BA patients with mild liver fibrosis (P< 0.01). Hepatic CDH11 mRNA levels were positively correlated with serum levels of γ-glutamyl transferase, total bilirubin, direct bilirubin and bile acid in children with BA (r= 0.26 ~ 0.37, all P< 0.05). Conclusions The mRNA levels of CDH11 were significantly increased in livers of BA patients compared to CC patients. The expression levels of CDH11 were associated with the progression of liver fibrosis and degree of liver injury in BA.
Key words: biliary atresia; cadherin-11; liver fibrosis; liver injury
| [1] | Wang J, Xu Y, Chen Z, et al. Liver immune profiling reveals pathogenesis and therapeutics for biliary atresia[J]. Cell, 2020, 183(7):1867-1883. |
| [2] | Ortiz-Perez A, Donnelly B, Temple H, et al. Innate immunity and pathogenesis of biliary atresia[J]. Front Immunol, 2020, 11:329. |
| [3] | Xiao Y, Liu R, Li X, et al. Long noncoding RNA H19 contributes to cholangiocyte proliferation and cholestatic liver fibrosis in biliary atresia[J]. Hepatology, 2019, 70(5):1658-1673. |
| [4] | Zhou K, Xie G, Wen J, et al. Histamine is correlated with liver fibrosis in biliary atresia[J]. Dig Liver Dis, 2016, 48(8):921-926. |
| [5] | Okubo R, Nio M, Sasaki H, et al. Impacts of early kasai portoenterostomy on short-term and long-term outcomes of biliary atresia[J]. Hepatol Commun, 2021, 5(2):234-243. |
| [6] | Birtolo C, Pham H, Morvaridi S, et al. Cadherin-11 is a cell surface marker up-regulated in activated pancreatic stellate cells and is involved in pancreatic cancer cell migration[J]. Am J Pathol, 2017, 187(1):146-155. |
| [7] | Chen X, Xiang H, Yu S, et al. Research progress in the role and mechanism of Cadherin-11 in different diseases[J]. J Cancer, 2021, 12(4):1190-1199. |
| [8] | Lodyga M, Cambridge E, Karvonen HM, et al. Cadherin-11-mediated adhesion of macrophages to myofibroblasts establishes a profibrotic niche of active TGF-β[J]. Sci Signal, 2019, 12(564):eaao3469. |
| [9] | Franzè E, Monteleone I, Laudisi F, et al. Cadherin-11 Is a Regulator of Intestinal Fibrosis[J]. J Crohns Colitis, 2020, 14(3):406-417. |
| [10] | 杨媛, 孙超, 高伟, 等. 胆道闭锁诊断及治疗指南(2018版)[J]. 临床肝胆病杂志, 2019, 35(11):2435-2440. |
| [11] | 中华医学会外科学分会胆道外科学组. 胆管扩张症诊断与治疗指南(2017版)[J]. 中华消化外科杂志, 2017, (16):767-774. |
| [12] | Ishibashi H, Shimada M, Kamisawa T, et al. Japanese clinical practice guidelines for congenital biliary dilatation[J]. J Hepatobiliary Pancreat Sci, 2017, 24(1):1-16. |
| [13] | Luo Y, Brigham D, Bednarek J, et al. Unique Cho-langiocyte-targeted IgM autoantibodies correlate with poor outcome in biliary atresia[J]. Hepatology, 2021, 73(5):1855-1867. |
| [14] | Schroer AK, Bersi MR, Clark CR, et al. Cadherin-11 blockade reduces inflammation-driven fibrotic remodeling and improves outcomes after myocardial infarction[J]. JCI Insight, 2019, 4(18):e131545. |
| [15] | Kisseleva T, Brenner D. Molecular and cellular mecha-nisms of liver fibrosis and its regression[J]. Nat Rev Gastroenterol Hepatol, 2021, 18(3):151-166. |
| [16] | Dewidar B, Meyer C, Dooley S, et al. TGF-beta in hepatic stellate cell activation and liver fibrogenesis-updated 2019[J]. Cells, 2019, 8(11):1419. |
| [17] | Cao W, Song S, Fang G, et al. Cadherin-11 deficiency attenuates ang-II-induced atrial fibrosis and susceptibility to atrial fibrillation[J]. J Inflamm Res, 2021, 14:2897-2911. |
| [18] | Pedroza M, To S, Smith J, et al. Cadherin-11 contributes to liver fibrosis induced by carbon tetrachloride[J]. PLoS One, 2019, 14(7):e0218971. |
| [19] | 周艳芬, 邬平, 李欣, 等. 血清GGT、DB在胆道闭锁和胆汁淤积症患儿中的水平变化及意义[J]. 山东医药, 2020, 60(31):15-18. |
/
| 〈 |
|
〉 |