Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (9): 148-154.doi: 10.6040/j.issn.1671-7554.0.2021.0865

Previous Articles    

Effects of U0126 on MEK/ERK/NF-κB pathway, proliferation and invasion in rats with endometriosis

WANG Fang1, CHEN Hua2, SHANG Lihong1, LI Ruyue1, LI Yongmei1, YANG Yu,e1, HA Chunfang2, 3   

  1. 1. Clinical College of Ningxia Medical University, Yinchuan 750004, Ningxia, China;
    2. Gynecology Department, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China;
    3. Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Yinchuan 750004, Ningxia, China
  • Published:2021-10-15

RichHTML

4

PDF (PC)

209

Abstract: Objective To investigate the effects of U0126 on MEK/ERK/NF-κB pathway, proliferation and invasion in rats with endometriosis. Methods After autologous transplantation of endometriosis rat models were successfully established, 18 female SD rats were randomly divided into the model group, dimethyl sulfoxide(DMSO)group, U0126 group(20 mg/kg), and control group(sham operation group), with 6 rats in each group. The rats were sacrificed after 4 weeks of medication. The volume of endometriosis lesions were measured and calculated. HE staining was used to observe the pathological changes of the endometrium. Immunohistochemical staining and Western blotting were used to detect the expressions of proliferating cell nuclear antigen(PCNA), matrix metalloproteinase 9(MMP9), MEK, ERK and NF-κB in the eutopic endometrial tissues. Results Compared with the model group, U0126 group had significantly reduced volume of ectopic lesions(F=4.54, P=0.02). HE staining results showed that in the control group, the endometrial glandular epithelium was arranged in columns, the gland cavity was intact and neatly arranged, and there was no bleeding or inflammatory cell formation around the glands. The model group and DMSO group showed multiple endometriotic gland cysts and interstitial reactions of varying sizes, with a large amount of inflammatory cell infiltration, bleeding and new growth around the glands and angiogenesis. Compared with the model group, U0126 group had significantly smaller endometrial glands and glandular cavity, thinner glandular epithelium, and less interstitial reaction. The results of immunohistochemistry showed that compared with the control group, model group and DMSO group had significantly increased expressions of PCNA and MMP9 in the eutopic endometrial tissues (P<0.05); compared with the model group, U0126 group had significantly reduced protein expression of PCNA and MMP9(P<0.05). There were no statistically significant differences in the DMSO group(P>0.05). Western blotting indicated that compared with the control group, model group and DMSO group had significantly increased expressions of MEK, ERK and NF-κB in the eutopic endometrial tissues(P<0.05); Compared with the model group, U0126 group had significantly reduced expressions of MEK, ERK and NF-κB(P<0.05), while there were no significant differences in the DMSO group(P>0.05). Conclusion U0126 can significantly inhibit the growth of ectopic lesions and glandular hyperplasia in endometriosis rats, and the mechanism may be related to the inhibition of MEK/ERK/NF-κB pathway to reduce the proliferation and invasion of eutopic endometrial tissues.

Key words: MEK/ERK signaling pathway, Nuclear transcription factor κB, Proliferating cell nuclear antigen, Matrix metalloproteinase 9

CLC Number: 

  • R711.71
[1] Gruber TM, Sylvia M. Pathogenesis of Endometriosis: The Origin of Pain and Subfertility [J]. Cells, 2021, 10(6): 1381.
[2] Leone Roberti Maggiore U, Ferrero S, Mangili G, et al. A systematic review on endometriosis during pregnancy: diagnosis, misdiagnosis, complications and outcomes [J]. Hum Reprod Update, 2016, 22(1): 70-103.
[3] Vercellini P, Viganò P, Somigliana E, et al. Endometriosis: pathogenesis and treatment [J]. Nat Rev Endocrinol, 2014, 10(5): 261-275.
[4] Filby CE, Rombauts L, Montgomery GW, et al. Cellular origins of endometriosis: towards novel diagnostics and therapeutics [J]. Semin Reproductive Med, 2020, 38(2/3): 201-215.
[5] Bafort C, Beebeejaun Y, Tomassetti C, et al. Laparoscopic surgery for endometriosis [J]. Cochrane Database Syst Rev, 2020, 10: CD01103. doi:10.1002/14651858.
[6] Tamhane N, Roberts B, Wiegand L, et al. Robotic surgery for urologic deep infiltrating endometriosis: a review and case presentations [J]. Surg Technol Int, 2020, 37: 154-160.
[7] PetryéR, Dresch DF, Carvalho C, et al. Oral glutamine supplementation attenuates inflammation and oxidative stress-mediated skeletal muscle protein content degradation in immobilized rats: Role of 70 kDa heat shock protein [J]. Free Radic Biol Med, 2019, 145: 87-102. doi: 10.1016/j.freeradbio med.2019.08.033.
[8] Jiang KF, Zhao G, Deng GZ, et al. Polydatin ameliorates Staphylococcus aureus-induced mastitis in mice via inhibiting TLR2-mediated activation of the p38 MAPK/NF-κB pathway [J]. Acta Pharmacol Sin, 2017, 38(2): 211-222.
[9] Li Y, Li R, Ouyang N, et al. Investigating the impact of local inflammation on granulosa cells and follicular development in women with ovarian endometriosis [J]. Fertil Steril, 2019, 112(5): 882-891.
[10] 王芳, 杨玉娥, 李茹月, 等. CHI3L1与MMP9在子宫内膜异位症大鼠内膜中的表达及意义[J]. 宁夏医科大学学报,2021, 43(6): 614-619.
[11] Sutrisno S, Sulistyorini C, Manungkalit EM, et al. The effect of genistein on TGF-β signal, dysregulation of apoptosis, cyclooxy genase-2 pathway, and NF-kB pathway in mice peritoneum of endometriosis model [J]. Middle East Fertility Society Journal, 2017, 22(4): 295-299.
[12] McCluggage WG. Endometriosis-related pathology: a discussion of selected uncommon benign, premalignant and malignant lesions [J]. Histopathology, 2020, 76(1): 76-92.
[13] Arcoverde F, Andres MP, Souza CC, et al. Deep endometriosis: medical or surgical treatment? [J]. Minerva Obstet Gynecol, 2021, 73(3): 341-346.
[14] Yuan J, Zhang J, Cao J, et al. Geniposide alleviates traumatic brain injury in rats via anti-inflammatory effect and MAPK/NF-kB inhibition [J]. Cell Mol Neurobiol, 2020, 40(4): 511-520.
[15] El-Agamy DS, El-Harbi KM, Khoshhal S, et al. Pristimerin protects against doxorubicin-induced cardiotoxicity and fibrosis through modulation of Nrf2 and MAPK/ NF-kB signaling pathways [J]. Cancer Manag Res, 2019, 11: 47-61. doi: 10. 2147/cmar.s186696.
[16] Uimari O, Rahmioglu N, Nyholt DR, et al. Genome-wide genetic analyses highlight mitogen-activated protein kinase(MAPK)signaling in the pathogenesis of endometriosis [J]. Hum Reprod, 2017, 32(4): 780-793.
[17] 丑丹, 黄艳辉, 冯丹, 等. 温经止痛合剂对子宫内膜异位症大鼠MAPK信号通路的影响[J]. 中华中医药杂志, 2021, 36(7): 3807-3811. CHOU Dan, HUANG Yanhui, FENG Dan, et al. Effects of Wenjing Zhitong Mixture on MAPK signaling pathway in the endometriosis model rats [J]. China Journal of Traditional Chinese Medicine and Pharmacy, 2021, 36(7): 3807-3811.
[18] 谢韬, 曾薇薇, 陆齐天, 等. 信号通路调控子宫内膜异位症的研究进展[J]. 国际妇产科学杂志, 2021, 48(1): 1-4. XIE Tao, ZENG Weiwei, LU Qitian, et al. Advances in research on signaling pathways regulation of endometriosis [J]. Journal of International Obstetrics And Gynecology, 2021, 48(1): 1-4.
[19] Bustami A, Sopiah P, Muharam R, et al. Effects of gallic acid and its derivates on inflammatory regulation of endo-metriotic primary cultures: study on NF-κB mRNA expression and IL-6 secretion [J]. Biomed Pharma J, 2018, 11(3): 1479-1484.
[20] 李博然, 马璐璐, 申乐, 等. NF-κB信号通路在子宫内膜异位症疼痛中作用的研究进展 [J]. 基础医学与临床, 2018, 38(10): 1466-1469. LI Boran, MA Lulu, SHEN Le, et al. Progress in nuclear factor-κB signaling pathway in the pathogenesis of endometriosis pain [J]. Basic and Clinical Medicine, 2018, 38(10): 1466-1469.
[21] 朱小琳, 韩亚光, 韩延华, 等. 子宫内膜异位症相关信号通路研究进展[J]. 国际妇产科学杂志, 2019, 46(4): 370-373. ZHU Xiaolin, HAN Yaguang, HAN Yanhua, et al. Advances in research on signaling pathway related to endometriosis [J]. Journal of International Obstetrics And Gynecology, 2019, 46(4):370-373.
[22] Simonneau L, Gallego M, Pujol R, et al. Comparative expression patterns of T-, N-, E-cadherins, beta-catenin, and polysialic acid neural cell adhesion molecule in rat cochlea during development: implications for the nature of Kölliker's organ [J]. J Comp Neurol, 2003, 459(2): 113-126.
[23] Li T, Quan H, Zhang H, et al. Silencing cyclophilin a improves insulin secretion, reduces cell apoptosis, and alleviates inflammation as well as oxidant stress in high glucose-induced pancreatic β-cells via MAPK/NF-kb signaling pathway [J]. Bioengineered, 2020, 11(1): 1047-1057.
[24] Arosh JA, Banu SK. Dual inhibition of ERK1/2 and AKT pathways is required to suppress the growth and survival of endometriotic cells and lesions [J]. Mol Cell Endocrinol, 2019, 484: 78-92. doi:10.1016/j.mce.2018.12.011.
[1] ZHAO Hongjian, ZHOU Jijun, SU Qingliang, ZHAO Shuo, LI Yuming. Correlation between human gastric cancer mesenchymal stem cells and tumor progression in SGC-7901 tumor-bearing mice [J]. Journal of Shandong University (Health Sciences), 2019, 57(9): 69-73.
[2] YU Lei, LI Zhen. Expression of interleukin-33 and its function in the serum of patients with cerebrovascular disease [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(4): 75-79.
[3] LIU Bo, YANG Wei, MU Cheng-zhi, ZHANG Yu-bao, XU Guang-ming. Effects of troglitazone on the expressions of CD147,  TGF-β1 and MMP-9 in GH3 cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(3): 6-9.
[4] WANG Lei-yan1, SONG Shang-ming1, ZHANG Hong-yu2, YOU Bei-an2, TANG Yuan-sheng1, CUI Lian-qun1, ZHU Xing-lei1. Effect of co-transfection of VEGF and PCNA-ASODN on restenosis after  percutaneous transluminal coronary angioplasty [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2011, 49(5): 38-42.
[5] LIU He,ZOU Xue,LI Min,WU Xiao-juan,ZHANG Li-qiang,YE Ping,LI Xue-zhong. Expression of MMP-9 and PCNA in sinonasal inverted papilloma and the clinical significance [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(3): 233-237.
[6] LAI Li-ping,ZHANG Ji-dong,LI Li-zhen,LIU Fen-ye. Inhibitory effect of the Yishenhuoxue Capsule on the proliferation of vascular smooth muscle cells induced by HCY in rabbits [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(10): 1011-1015.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] . [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(10): 995 .
[2] JIANG Hong-ju,LI Run-zhi, WANG Ying,XU Dong-mei,ZHANG Mei,ZHANG Yun,LI Ji-fu. Relationship between the plasma level of matrix metalloproteinase-9 and structural characteristics of plaques and percutaneous coronary intervention [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(10): 966 -970 .
[3] ZHENG Min,HAO Yue-wei,LIU Xue-ping,ZHAO Ting-ting. Relationship between the HPA-2 and Kozak sequence polymorphism of platelet membrane glycoprotein and cerebral infarction[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(3): 292 -295 .
[4] ZHANG Jie,LI Zhen-hua,SUN Jin-hao,BAO Li-hua,LIU Yue-peng. Protective effects of the invariable magnetic field on oxidative injured Schwann cells[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(3): 229 -232 .
[5] . [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(8): 828 -830 .
[6] . [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(9): 5 -6 .
[7] NIU Rui,LIU Bo,SHAO Ming-ju,WANG Wei. mRNA expression of lunx in regional lymph nodes of non-small cell lung cancer and its correlation with prognosis[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(9): 884 -885 .
[8] ZHAO Peng,BI Wan-li,LI Ning. Post-processing techniques of spiral CT in adolescent congenital spinal deformity[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(8): 825 -829 .
[9] WANG Shu-qin,QI Feng,WU Jian-bo,SUN Bao-zhu. Effect of calcium in ropivacaine-induced smooth muscle contraction of the aorta in rats in vitro[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(8): 773 -776 .
[10] TENG Xue-ren,ZHAO Yong-sheng,HU Guang-liang,ZHOU Lun,LI Jian-min. Characteristics of microcosmic changes following tendon allograft transplantation preserved by two methods under light microscopy and transmission electron microscopy[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(10): 945 -950 .
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd