β-catenin在慢性移植肾肾损伤中的作用
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摘要
目的:探讨β-catenin在慢性移植肾肾损伤中的作用。方法:选取诊断为慢性移植肾肾损伤的肾活检标本30例和正常肾组织10例做对照;用免疫组织化学法检测肾活检组织中β-catenin,CD163(标记M2型巨噬细胞)和SMA蛋白的表达情况;用Masson染色法评估肾活检组织的间质纤维化程度;分析肾活检组织中β-catenin与CD163、移植肾间质纤维化程度及患者血肌酐(Cr)水平的关系。结果:移植肾组织中的β-catenin、CD163和SMA显著高于正常肾组织(P<0.05);随着移植肾间质纤维化程度的加重,移植肾组织中β-catenin和CD163的表达逐渐增多,患者血肌酐和尿素氮水平也逐渐升高(P<0.05);移植肾组织中β-catenin和CD163的表达呈正相关,与患者血肌酐水平呈正相关(P<0.001)。结论:β-catenin和CD163阳性的M2型巨噬细胞在慢性移植肾肾损伤组织中异常高表达,并且与移植肾间质纤维化程度和肾移植患者肾功能不全相关。
Objective: To investigate the role of β-catenin in chronic kidney allograft injury. Methods: By using immunohistochemical staining method, the levels of β-catenin, CD163 and SMA expression were detected in the renal biopsy tissues of 30 cases of CAI and 10 cases of normal kidney. The degree of interstitial fibrosis in renal biopsy tissues was assessed by Masson staining. The relationship between β-catenin and CD163, the degree of interstitial fibrosis and serum creatinine level in patients was analysed. Results: There were statistically significant differences in expression of β-catenin, CD163 and SMA between kidney allograft and normal kidney tissue(P<0.05); with the increase of renal fibrosis severity, the levels of serum Cr, BUN and the expression of β-catenin and CD163 were increased(P<0.05); the β-catenin protein was positively correlated with the expression of CD163 and serum creatinine(P<0.001). Conclusion: The abnormal high expression of β-catenin and CD163 positive(M2 macrophages) in chronic kidney allograft injury are associated with the degree of interstitial fibrosis and renal insufficiency in patients.
Objective: To investigate the role of β-catenin in chronic kidney allograft injury. Methods: By using immunohistochemical staining method, the levels of β-catenin, CD163 and SMA expression were detected in the renal biopsy tissues of 30 cases of CAI and 10 cases of normal kidney. The degree of interstitial fibrosis in renal biopsy tissues was assessed by Masson staining. The relationship between β-catenin and CD163, the degree of interstitial fibrosis and serum creatinine level in patients was analysed. Results: There were statistically significant differences in expression of β-catenin, CD163 and SMA between kidney allograft and normal kidney tissue(P<0.05); with the increase of renal fibrosis severity, the levels of serum Cr, BUN and the expression of β-catenin and CD163 were increased(P<0.05); the β-catenin protein was positively correlated with the expression of CD163 and serum creatinine(P<0.001). Conclusion: The abnormal high expression of β-catenin and CD163 positive(M2 macrophages) in chronic kidney allograft injury are associated with the degree of interstitial fibrosis and renal insufficiency in patients.
引文
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20.Gewin LS.Renal tubule repair:is Wnt/β-catenin a friend or foe?[J].JGenes(Basel),2018,9(2):E58.
2.Haas M,Loupy A,Lefaucheur C,et al.The Banff 2017 Kidney Meeting Report:Revised diagnostic criteria for chronic active T cell-mediated rejection,antibody-mediated rejection,and prospects for integrative endpoints for next-generation clinical trials[J].Am J Transplant,2018,18(2):293-307.
3.Pan B,Liu G,Jiang Z,et al.Regulation of renal fibrosis by macrophage polarization[J].Cell Physiol Biochem,2015,35(3):1062-1069.
4.Ikezumi Y,Suzuki T,Yamada T,et al.Alternatively activated macrophages in the pathogenesis of chronic kidney allograft injury[J].Pediatr Nephrol,2015,30(6):1007-1017.
5.Solez K,Colvin RB,Racusen LC,et al.Banff'05 Meeting Report:differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy('CAN')[J].Am J Transplant,2007,7(3):518-526.
6.Zhou D,Tan RJ,Fu H,et al.Wnt/β-catenin signaling in kidney injury and repair:A double-edged sword[J].Lab Invest,2016,96(2):156-167.
7.Lin SL,Li B,Rao S,et al.Macrophage Wnt7b is critical for kidney repair and regeneration[J].Proc Natl Acad Sci USA,2010,107(9):4194-4199.
8.Zhou D,Tan RJ,Zhou L,et al.Kidney tubularβ-catenin signaling controls interstitial fibroblast fate via epithelial-mesenchymal communication[J].Sci Rep,2013,3:1878.
9.Liu G,Yang H.Modulation of macrophage activation and programming in immunity[J].J Cell Physiol,2013,228(3):502-512.
10.Mantovani A,Biswas SK,Galdiero MR,et al.Macrophage plasticity and polarization in tissue repair and remodelling[J].J Pathol,2013,229(2):176-185.
11.Klessens CQF,Zandbergen M,Wolterbeek R,et al.Macrophages in diabetic nephropathy in patients with type 2 diabetes[J].Nephrol Dial Transplant,2017,32(8):1322-1329.
12.Wang YY,Jiang H,Pan J,et al.Macrophage-to-myofibroblast transition contributes to interstitial fibrosis in chronic renal allograft injury[J].JAm Soc Nephrol,2017,28(7):2053-2067.
13.姜莹莹,杜玄一.肾间质纤维化中肌成纤维细胞来源的研究进展[J].临床荟萃,2015,30(3):49-352.JIANG Yingying,DU Xuanyi.Progress in research on the origin of myofibroblasts in renal interstitial fibrosis[J].Clinical Focus,2015,30(3):349-352.
14.Maarouf OH,Aravamudhan A,Rangarajan D,et al.Paracrine Wnt1drives interstitial fibrosis without inflammation by tubulointerstitial cross-talk[J].J Am Soc Nephrol,2016,27(3):781-790.
15.Xiao L,Zhou D,Tan RJ,et al.Sustained activation of Wnt/β-catenin signaling drives AKI to CKD progression[J].J Am Soc Nephrol,2016,27(6):1727-1740.
16.Zhou D,Fu H,Zhang L,et al.Tubule-derived Wnts are required for fibroblast activation and kidney fibrosis[J].J Am Soc Nephrol,2017,28(8):2322-2336.
17.Rogers NM,Ferenbach DA,Isenberg JS,et al.Dendritic cells and macrophages in the kidney:A spectrum of good and evil[J].Nat Rev Nephrol,2014,10(11):625-643.
18.Amini-Nik S,Cambridge E,Yu W,et al.β-catenin-regulated myeloid cell adhesion and migration determine wound healing[J].J Clin Invest,2014,124(6):2599-2610.
19.Feng Y,Ren J,Gui Y,et al.Wnt/β-catenin-promoted macrophage alternative activation contributes to kidney fibrosis[J].J Am Soc Nephrol,2018,29(1):182-193.
20.Gewin LS.Renal tubule repair:is Wnt/β-catenin a friend or foe?[J].JGenes(Basel),2018,9(2):E58.