Musashi-1和β-catenin在子宫内膜中的表达及其在内膜异位病灶形成中的作用
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摘要
目的:检测Musashi-1和β-连环蛋白(β-catenin)在子宫内膜异位症(EMs)患者的在位内膜和异位内膜中的表达,并初步探讨作用机制。方法:2016年9月至2018年9月,收集EMs患者的在位内膜(在位内膜组,28例)、异位内膜(异位内膜组,24例)和非EMs患者的正常内膜(正常内膜组,30例),采用实时荧光定量PCR(Real-time PCR)试验检测Musashi-1和β-catenin在各组内膜组织中的表达情况,并分析Musashi-1和β-catenin在各组内膜组织中的表达相关关系。结果:在位内膜组和异位内膜组中,Musashi-1和β-catenin的相对表达量均明显高于正常内膜组(P<0.05),而在位内膜组与异位内膜组之间的差异无统计学意义(P>0.05)。在位内膜组和正常内膜组中,增生期的Musashi-1和β-catenin相对表达量显著高于分泌期(P<0.05),而异位内膜组中,在增生期和分泌期Musashi-1和β-catenin比较差异无统计学意义(P>0.05)。在位内膜组和异位内膜组中,Musashi-1和β-catenin表达之间均呈正相关性(P<0.05),而正常内膜组中,两者表达之间无明显相关性(P>0.05)。结论:在EMs的发病过程中,干细胞标志物Musashi-1可能通过激活Wnt/β-catenin信号通路参与并促进子宫内膜异位病灶的形成。
Objective: To detect the expressions of Musashi-1 and β-catenin in the eutopic endometrium and ectopic endometrium of patients with endometriosis(EMs), and to preliminarily explore the possible mechanism. Methods: Eutopic endometrium of patients with EMs(eutopic endometrium group, 28 cases), ectopic endometrium of patients with EMs(ectopic endometrium group, 24 cases) and normal endometrium of people without EMs(normal endometrium group, 30 cases) were collected during September 2016 to September 2018. The expression of Musashi-1 and β-catenin in the endometrium tissue of each group was detected by real time fluorescence quantitative PCR(Real-time PCR) test, and the correlation between the expression of Musashi-1 andβ-catenin in the endometrium tissue of each group was analyzed. Results: The relative expression quantity of Musashi-1 and β-catenin in the eutopic endometrium group and the ectopic endometrium group was significantly higher than those in the normal endometrium group(P<0.05), while there was no difference between the eutopic endometrium group and the ectopic endometrium group(P>0.05).In the eutopic endometrium group and the normal endometrium group, the relative expression quantity of Musashi-1 and β-catenin in the proliferative period was significantly higher than those in the secretory period(P<0.05), but there was no difference between the proliferative period and the secretory period in the ectopic endometrium group(P>0.05). There was a positive correlation between the expression of Musashi-1 and β-catenin in the eutopic endometrium group and the ectopic endometrium group(P<0.05), but there was no correlation between the expression of Musashi-1 and β-catenin in the normal endometrium group(P >0.05). Conclusion: In the pathogenesis of EMs, stem cell marker Musashi-1 may participate in and promote the formation of endometriosis lesions by activating Wnt/β-catenin signaling pathway.
Objective: To detect the expressions of Musashi-1 and β-catenin in the eutopic endometrium and ectopic endometrium of patients with endometriosis(EMs), and to preliminarily explore the possible mechanism. Methods: Eutopic endometrium of patients with EMs(eutopic endometrium group, 28 cases), ectopic endometrium of patients with EMs(ectopic endometrium group, 24 cases) and normal endometrium of people without EMs(normal endometrium group, 30 cases) were collected during September 2016 to September 2018. The expression of Musashi-1 and β-catenin in the endometrium tissue of each group was detected by real time fluorescence quantitative PCR(Real-time PCR) test, and the correlation between the expression of Musashi-1 andβ-catenin in the endometrium tissue of each group was analyzed. Results: The relative expression quantity of Musashi-1 and β-catenin in the eutopic endometrium group and the ectopic endometrium group was significantly higher than those in the normal endometrium group(P<0.05), while there was no difference between the eutopic endometrium group and the ectopic endometrium group(P>0.05).In the eutopic endometrium group and the normal endometrium group, the relative expression quantity of Musashi-1 and β-catenin in the proliferative period was significantly higher than those in the secretory period(P<0.05), but there was no difference between the proliferative period and the secretory period in the ectopic endometrium group(P>0.05). There was a positive correlation between the expression of Musashi-1 and β-catenin in the eutopic endometrium group and the ectopic endometrium group(P<0.05), but there was no correlation between the expression of Musashi-1 and β-catenin in the normal endometrium group(P >0.05). Conclusion: In the pathogenesis of EMs, stem cell marker Musashi-1 may participate in and promote the formation of endometriosis lesions by activating Wnt/β-catenin signaling pathway.
引文
[1] Kim HW, Yoo JE. Inhibitory effect of traditional Korean medicine on the recurrent endometriosis after laparoscopic excision:a case report[J]. Integr Med Res, 2018, 7(3):296-301
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[3] Berger J, Henneman O, Rhemrev J, et al. MRI-Ultrasound Fusion Imaging for Diagnosis of Deep Infiltrating Endometriosis-A Critical Appraisal[J]. Ultrasound Int Open, 2018, 4(3):E85-E90
[4] Ciavattini A, Delli Carpini G, Serri M, et al. Unfolded protein response, a link between endometrioid ovarian carcinoma and endometriosis:A pilot study[J]. Oncol Lett, 2018, 16(4):5449-5454
[5] Lee YH, Yang JX, Allen JC, et al. Elevated peritoneal fluid ceramides in human endometriosis-associated infertility and their effects on mouse oocyte maturation[J]. Fertil Steril, 2018, 110(4):767-777
[6] Krishnakumar S, Krishnakumar R, Hiwale S. Pregnancy through Assisted Reproductive Technology in a Patient with Thoracic Endometriosis Syndrome[J]. J Hum Reprod Sci, 2018, 11(2):198-201
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[9] Yu CX, Song JH, Liang L. Correlation of changes of(non)exfoliated endometrial organelles and expressions of Musashi-1 andβ-catenin with endometriosis in menstrual period[J]. Gynecol Endocrinol, 2014,30(12):861-867
[10] Wang C, Zhang J, Fok KL, et al. CD147 Induces Epithelial-toMesenchymal Transition by Disassembling Cellular Apoptosis Susceptibility Protein/E-Cadherin/β-Catenin Complex in Human Endometriosis[J]. Am J Pathol, 2018, 188(7):1597-1607
[11]宁丽,陈萱,庄如锦,等.子宫内膜异位症发病机制的研究进展[J].现代生物医学进展, 2016, 16(3):593-596, 556
[12] Jaiman S, Pochiraju M, Gundabattula SR, et al. Malignant Transformation of Pelvic Endometriosis:Case Series and Review of the Literature[J]. Int J Surg Pathol, 2015, 23(6):465-471
[13] Hirsch M, JMN D, Kusznir JO, et al. Variation in outcome reporting in endometriosis trials:a systematic review[J]. Am J Obstet Gynecol,2016, 214(4):452-464
[14] Luckow Invitti A, Schor E, Martins Parreira R, et al. Inflammatory cytokine profile of co-cultivated primary cells from the endometrium of women with and without endometriosis[J]. Mol Med Rep, 2018, 18(2):1287-1296
[15] Li F, Alderman MH, Tal A, et al. Hematogenous Dissemination of Mesenchymal Stem Cells from Endometriosis[J]. Stem Cells, 2018,36(6):881-890
[16] Abreu JP, Rebelatto CLK, Savari CA, et al. The Effect of Mesenchymal Stem Cells on Fertility in Experimental Retrocervical Endometriosis[J]. Rev Bras Ginecol Obstet, 2017, 39(5):217-223
[17]杨云.子宫内膜干细胞学说在子宫内膜异位症中的作用及研究进展[J].中国组织工程研究, 2016, 20(28):4250-4256
[18] Koippallil Gopalakrishnan AR, Kishore U, Madan T. Mesenchymal stem cells:a promising tool for targeted gene therapy of endometriosis[J]. Regen Med, 2017, 12(1):69-76
[19] Ma L, Xu YL, Ding WJ, et al. Prognostic value of Musashi-1 in endometrioid adenocarcinoma[J]. Int J Clin Exp Pathol, 2015, 8(5):4564-4572
[20] G觟tte M, Wolf M, Staebler A, et al. Increased expression of the adult stem cell marker Musashi-1 in endometriosis and endometrial carcinoma[J]. J Pathol, 2008, 215(3):317-329
[21]郎景和.子宫内膜异位症的研究与设想[J].中华妇产科杂志,2003,38(8):478-480
[22] Zhang L, Xiong W, Xiong Y, et al. 17β-Estradiol promotes vascular endothelial growth factor expression via the Wnt/β-catenin pathway during the pathogenesis of endometriosis[J]. Mol Hum Reprod, 2016,22(7):526-535
[23] Zhu X, Li Y, Zhou R, et al. Knockdown of E-cadherin expression of endometrial epithelial cells may activate Wnt/β-catenin pathway in vitro[J]. Arch Gynecol Obstet, 2018, 297(1):117-123
[24] Zanatta A, Pereira RM, Rocha AM, et al. The relationship among HOXA10, estrogen receptorα, progesterone receptor,and progesterone receptor B proteins in rectosigmoid endometriosis:a tissue microarray study[J]. Reprod Sci, 2015, 22(1):31-37
[25]洪星辉,黄金玲.Wnt/β连环素和NF-κB信号通路对磷脂酶D的调控作用及其与肿瘤关系的研究进展[J].中国药理学与毒理学杂志, 2014, 28(5):779-783
[26] Xu H, Yang JJ, Wang CH, et al. Effect of Wnt/β-catenin signal pathway on of matrix metalloproteinase-7 and vascular endothelial growth factor gene expressions in endometriosis[J]. Clin Exp Obstet Gynecol, 2016, 43(4):573-577
[27] de Mattos RM, Pereira PR, Barros EG, et al. Aberrant levels of Wnt/β-catenin pathway components in a rat model of endometriosis[J]. Histol Histopathol, 2016, 31(8):933-942
[28] Rath G, Jawanjal P, Salhan S, et al. Clinical significance of inactivated glycogen synthase kinase 3βin HPV-associated cervical cancer:Relationship with Wnt/β-catenin pathway activation[J]. Am J Reprod Immunol, 2015, 73(5):460-478
[29]刘鑫,王化丽,王悦阳,等.雌激素对子宫内膜异位症患者在位子宫内膜间质细胞合成NGF及COX-2的影响及传导通路研究[J].中国妇幼健康研究, 2017, 28(1):51-53, 65
[30] Kulak J, Fischer C, Komm B, et al. Treatment with bazedoxifene,a selective estrogen receptor modulator,causes regression of endometriosis in a mouse model[J]. Endocrinology, 2011, 152(8):3226-3232
[2] Yoldemir T. Quality of life for women with endometriosis:premenopausal and postmenopausal perspectives[J]. Climacteric,2018, 21(5):411-412
[3] Berger J, Henneman O, Rhemrev J, et al. MRI-Ultrasound Fusion Imaging for Diagnosis of Deep Infiltrating Endometriosis-A Critical Appraisal[J]. Ultrasound Int Open, 2018, 4(3):E85-E90
[4] Ciavattini A, Delli Carpini G, Serri M, et al. Unfolded protein response, a link between endometrioid ovarian carcinoma and endometriosis:A pilot study[J]. Oncol Lett, 2018, 16(4):5449-5454
[5] Lee YH, Yang JX, Allen JC, et al. Elevated peritoneal fluid ceramides in human endometriosis-associated infertility and their effects on mouse oocyte maturation[J]. Fertil Steril, 2018, 110(4):767-777
[6] Krishnakumar S, Krishnakumar R, Hiwale S. Pregnancy through Assisted Reproductive Technology in a Patient with Thoracic Endometriosis Syndrome[J]. J Hum Reprod Sci, 2018, 11(2):198-201
[7] Gordts S, Koninckx P, Brosens I. Pathogenesis of deep endometriosis[J]. Fertil Steril, 2017, 108(6):872-885
[8]王颜,樊利芳.干细胞基因Musashi-1研究进展[J].中国肿瘤临床,2014, 41(4):269-271
[9] Yu CX, Song JH, Liang L. Correlation of changes of(non)exfoliated endometrial organelles and expressions of Musashi-1 andβ-catenin with endometriosis in menstrual period[J]. Gynecol Endocrinol, 2014,30(12):861-867
[10] Wang C, Zhang J, Fok KL, et al. CD147 Induces Epithelial-toMesenchymal Transition by Disassembling Cellular Apoptosis Susceptibility Protein/E-Cadherin/β-Catenin Complex in Human Endometriosis[J]. Am J Pathol, 2018, 188(7):1597-1607
[11]宁丽,陈萱,庄如锦,等.子宫内膜异位症发病机制的研究进展[J].现代生物医学进展, 2016, 16(3):593-596, 556
[12] Jaiman S, Pochiraju M, Gundabattula SR, et al. Malignant Transformation of Pelvic Endometriosis:Case Series and Review of the Literature[J]. Int J Surg Pathol, 2015, 23(6):465-471
[13] Hirsch M, JMN D, Kusznir JO, et al. Variation in outcome reporting in endometriosis trials:a systematic review[J]. Am J Obstet Gynecol,2016, 214(4):452-464
[14] Luckow Invitti A, Schor E, Martins Parreira R, et al. Inflammatory cytokine profile of co-cultivated primary cells from the endometrium of women with and without endometriosis[J]. Mol Med Rep, 2018, 18(2):1287-1296
[15] Li F, Alderman MH, Tal A, et al. Hematogenous Dissemination of Mesenchymal Stem Cells from Endometriosis[J]. Stem Cells, 2018,36(6):881-890
[16] Abreu JP, Rebelatto CLK, Savari CA, et al. The Effect of Mesenchymal Stem Cells on Fertility in Experimental Retrocervical Endometriosis[J]. Rev Bras Ginecol Obstet, 2017, 39(5):217-223
[17]杨云.子宫内膜干细胞学说在子宫内膜异位症中的作用及研究进展[J].中国组织工程研究, 2016, 20(28):4250-4256
[18] Koippallil Gopalakrishnan AR, Kishore U, Madan T. Mesenchymal stem cells:a promising tool for targeted gene therapy of endometriosis[J]. Regen Med, 2017, 12(1):69-76
[19] Ma L, Xu YL, Ding WJ, et al. Prognostic value of Musashi-1 in endometrioid adenocarcinoma[J]. Int J Clin Exp Pathol, 2015, 8(5):4564-4572
[20] G觟tte M, Wolf M, Staebler A, et al. Increased expression of the adult stem cell marker Musashi-1 in endometriosis and endometrial carcinoma[J]. J Pathol, 2008, 215(3):317-329
[21]郎景和.子宫内膜异位症的研究与设想[J].中华妇产科杂志,2003,38(8):478-480
[22] Zhang L, Xiong W, Xiong Y, et al. 17β-Estradiol promotes vascular endothelial growth factor expression via the Wnt/β-catenin pathway during the pathogenesis of endometriosis[J]. Mol Hum Reprod, 2016,22(7):526-535
[23] Zhu X, Li Y, Zhou R, et al. Knockdown of E-cadherin expression of endometrial epithelial cells may activate Wnt/β-catenin pathway in vitro[J]. Arch Gynecol Obstet, 2018, 297(1):117-123
[24] Zanatta A, Pereira RM, Rocha AM, et al. The relationship among HOXA10, estrogen receptorα, progesterone receptor,and progesterone receptor B proteins in rectosigmoid endometriosis:a tissue microarray study[J]. Reprod Sci, 2015, 22(1):31-37
[25]洪星辉,黄金玲.Wnt/β连环素和NF-κB信号通路对磷脂酶D的调控作用及其与肿瘤关系的研究进展[J].中国药理学与毒理学杂志, 2014, 28(5):779-783
[26] Xu H, Yang JJ, Wang CH, et al. Effect of Wnt/β-catenin signal pathway on of matrix metalloproteinase-7 and vascular endothelial growth factor gene expressions in endometriosis[J]. Clin Exp Obstet Gynecol, 2016, 43(4):573-577
[27] de Mattos RM, Pereira PR, Barros EG, et al. Aberrant levels of Wnt/β-catenin pathway components in a rat model of endometriosis[J]. Histol Histopathol, 2016, 31(8):933-942
[28] Rath G, Jawanjal P, Salhan S, et al. Clinical significance of inactivated glycogen synthase kinase 3βin HPV-associated cervical cancer:Relationship with Wnt/β-catenin pathway activation[J]. Am J Reprod Immunol, 2015, 73(5):460-478
[29]刘鑫,王化丽,王悦阳,等.雌激素对子宫内膜异位症患者在位子宫内膜间质细胞合成NGF及COX-2的影响及传导通路研究[J].中国妇幼健康研究, 2017, 28(1):51-53, 65
[30] Kulak J, Fischer C, Komm B, et al. Treatment with bazedoxifene,a selective estrogen receptor modulator,causes regression of endometriosis in a mouse model[J]. Endocrinology, 2011, 152(8):3226-3232