Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (4): 55-61.doi: 10.6040/j.issn.1671-7554.0.2021.0472

Previous Articles    

Expressions and clinical significance of PARP-1 and HIF-1α in adenomyosis tissues and primary cells

XU Ge1, LI Qing1, ZHANG Cancan2, TIAN Yongjie1   

  1. 1. Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China;
    2. Department of Gynecology, Shandong Provincial Maternal and Child Health Care Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250014, Shandong, China
  • Published:2022-04-22

Abstract: Objective To explore the expressions and significance of poly(ADP-ribose)polymerase-1(PARP-1)and hypoxia inducible factor-1(HIF-1α)in adenomyosis(AM)tissues and normal endometrial tissues. Methods The expressions of PARP-1 and HIF-1α in the eutopic and ectopic endometria of women with AM and in normal endometria were detected with immunohistochemistry. The primary interstitial cells were extracted from the eutopic and ectopic endometria of patients with AM. After the expression of PARP-1 was knocked down, the change of HIF-1α expression was measured. Results Immunohistochemistry results showed that the expression of PARP-1 was higher in the eutopic(26/31 vs 4/10, P=0.006)and ectopic(24/31 vs 4/10, P=0.027)endometria of AM than in normal endometria; the expression of HIF-1α was higher in the eutopic(24/31 vs 3/10, P=0.006)and ectopic(23/31 vs 3/10, P=0.012)endometria of AM than in normal endometria. There was a positive correlation(r=0.357, P=0.038 in eutopic endometrial tissues; r=0.519, P=0.002 in ectopic endometrial tissues)between expressions of PARP-1 and HIF-1α, but there was no significant difference in the expressions of PARP-1(P=0.052)and HIF-1α(P=0.767)in the eutopic and ectopic endometria of adenomyosis. Western blotting results showed that the expression of PARP-1 in ectopic endometrial interstitial cells of AM was higher than that in eutopic endometrial interstitial cells(P=0.025), and PARP-1 was highly expressed in eutopic(P<0.001)and ectopic(P<0.001)endometrial interstitial cells of AM compared with normal endometrial interstitial cells. After PARP-1 knockdown, the expressionin eutopic endometria(t=4.786, P=0.003), ectopic endometria(t=9.458, P<0.001), and normal endometria(t=5.740, P=0.001)was significantly reduced, and the reduction of ectopic endometrial interstitial cells in AM was the most obvious. There was no significant difference in the expression of HIF-1α in eutopic and ectopic endometrial interstitial cells of AM(P=0.896), and the expression of HIF-1α in eutopic endometrial stromal cells(P<0.001)and ectopic endometrial stromal cells(P<0.001)was higher than that in normal endometrium interstitial cells. After PARP-1 knockdown, the expression of HIF-1α in eutopic endometria of AM(t=15.768, P<0.001), ectopic endometrial cells(t=3.459, P=0.025), and normal endometria(t=4.221 5, P=0.014)was significantly lower than before. Conclusion Both PARP-1 and HIF-1α may be involved in the development of AM, and the expression of PARP-1 may affect the expression of HIF-1α.

Key words: Adenomyosis, Poly(ADP-ribose)polymerase-1, Hypoxia inducible factor-1α, Poly(ADP-ribose)polymerase-1 inhibitor, Eutopic and ectopic endometria

CLC Number: 

  • R711.71
[1] Chapron C, Vannuccini S, Santulli P, et al. Diagnosing adenomyosis: an integrated clinical and imaging approach [J]. Hum Reprod Update, 2020, 26(3): 392-411.
[2] Munro MG. Classification and reporting systems for adenomyosis [J]. J Minim Invasive Gynecol, 2020, 27(2): 296-308.
[3] Bourdon M, Santulli P, Oliveira J, et al. Focal adenomyosis is associated with primary infertility [J]. Fertil Steril, 2020, 114(6): 1271-1277.
[4] Horton J, Sterrenburg M, Lane S, et al. Reproductive, obstetric, and perinatal outcomes of women with adenomyosis and endometriosis: a systematic review and meta-analysis [J]. Hum Reprod Update, 2019, 25(5): 592-632.
[5] Munro MG, Critchley HO, broder MS, et al. FIGO classification system(PALM-COEIN)for causes of abnormal uterine bleeding in nongravid women of reproductive age [J]. Int J Gynaecol Obstet, 2011, 113(1): 3-13.
[6] Harrision D, Gravells P, Thompson R, et al. Poly(ADP-Ribose)glycohydrolase(PARG)vs. poly(ADP-Ribose)polymerase(PARP)- function in genome maintenance and relevance of inhibitors for anti-cancer therapy [J]. Front Mol Biosci, 2020, 7: 191. doi: 10.3389/fmolb.2020.00191.
[7] Alemasova EE, Lavrik OI. Poly(ADP-ribosyl)ation by PARP1: reaction mechanism and regulatory proteins [J]. Nucleic Acids Res, 2019, 47(8): 3811-3827.
[8] 林雪艳, 李春艳, 侯小满, 等. PARP-1及EMT标志物在子宫腺肌病在位及异位内膜中的表达 [J]. 山东大学学报(医学版), 2017, 55(9): 36-40. LIN Xueyan, LI Chunyan, HOU Xiaoman, et al. Expressions of PARP-1 and EMT markers in eutopic and ectopic endometrium of adenomyosis [J]. Journal of Shandong University(Health Sciences), 2017, 55(9): 36-40.
[9] Prieto-Garcia E, Diaz-Garcia CV, Garcia-Ruiz I, et al. Epithelial-to-mesenchymal transition in tumor progression [J]. Med Oncol, 2017, 34(7): 122. doi: 10.1016/j.yexcr.2021.112791.
[10] Kang S, Zhao J, Liu Q, et al. Vascular endothelial growth factor gene polymorphisms are associated with the risk of developing adenomyosis [J]. Environ Mol Mutagen, 2009, 50(5): 361-366.
[11] Knight M, Stanley S. HIF-1alpha as a central mediator of cellular resistance to intracellular pathogens [J]. Curr Opin Immunol, 2019, 60(10): 111-116.
[12] Zhang FJ, Luo W, Lei GH. Role of HIF-1alpha and HIF-2alpha in osteoarthritis [J]. Joint Bone Spine, 2015, 82(3): 144-147.
[13] 薛源, 林雪艳, 徐歌, 等. 低氧诱导因子-1α在子宫内膜异位症患者血清中的表达和对在位子宫内膜间质细胞上皮-间质转化的影响 [J]. 山东大学学报(医学版), 2021, 59(2): 41-47. XUE Yuan, LIN Xueyan, XU Ge, et al. Expression of hypoxia-inducible factor-1α in the serum of patients with endometriosis and its effect on epithelial mesenchymal transition of eutopic endometrial stromal cells [J]. Journal of Shandong University(Health Sciences), 2021, 59(2): 41-47.
[14] Struble J, Reid S, Bedaiwy M. Adenomyosis: a clinical review of a challenging gynecologic condition [J]. J Minim Invasive Gynecol, 2016, 23(2): 164-185.
[15] Chen D, Qiao H, Wang Y, et al. Adenomyosis-derived extracellular vesicles endow endometrial epithelial cells with an invasive phenotype through epithelial-mesenchymal transition [J]. Genes Dis, 2020, 7(4): 636-648.
[16] Chen YJ, Li HY, Huang CH, et al. Oestrogen-induced epithelial-mesenchymal transition of endometrial epithelial cells contributes to the development of adenomyosis [J]. J Pathol, 2010, 222(3): 261-270.
[17] Leyendecker G, Wildt L, Mall G. The pathophysiology of endometriosis and adenomyosis: tissue injury and repair [J]. Arch Gynecol Obstet, 2009, 280(4): 529-538.
[18] Krishnakumar R, Kraus WL. The PARP side of the nucleus: molecular actions, physiological outcomes, and clinical targets [J]. Mol Cell, 2010, 39(1): 8-24.
[19] Kumar M, Jaiswal RK, Yadava PK, et al. An assessment of poly(ADP-ribose)polymerase-1 role in normal and cancer cells [J]. Biofactors, 2020, 46(6): 894-905.
[20] Kaufman B, Shapira-Frommer R, Schmutzler RK, et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation [J]. J Clin Oncol, 2015, 33(3): 244-250.
[21] Stark TW, Hensley PJ, Spwar A, et al. Predictive value of epithelial-mesenchymal-transition(EMT)signature and PARP-1 in prostate cancer radioresistance [J]. Prostate, 2017, 77(16): 1583-1591.
[22] Liu Y, Zhang Y, Zhao Y, et al. High PARP-1 expression is associated with tumor invasion and poor prognosis in gastric cancer [J]. Oncol Lett, 2016, 12(5): 3825-3835.
[23] Guo S, Zhang D, Lu X, et al. Hypoxia and its possible relationship with endometrial receptivity in adenomyosis: a preliminary study [J]. Reprod Biol Endocrinol, 2021, 19(1): 7. doi:10.1186/s12958-020-00692-y.
[24] Martínez-Romero R, Martínez-Lara E, Aguilar-Quesada R, et al. PARP-1 modulates deferoxamine-induced HIF-1alpha accumulation through the regulation of nitric oxide and oxidative stress [J]. J Cell Biochem, 2008, 104(6):2248-2260.
[25] Gonzalez-Flores A, Aguilar-Quesada R, Siles E, et al. Interaction between PARP-1 and HIF-2α in the hypoxic response [J]. Oncogene, 2014, 33(7): 891-898.
[26] Jaakkola P, Mole DR, Tian YM, et al. Targeting of HIF-alpha to the von hippel-lindau ubiquitylation complex by O2-regulated prolyl hydroxylation [J]. Science, 2001, 292(5516): 468-472.
[27] Buyn Y, Choi YC, Jeong Y, et al. MiR-200c downregulates HIF-1alpha and inhibits migration of lung cancer cells [J]. Cell Mol Biol Lett, 2019, 24: 28. doi:10.1186/s11658-019-0152-2.
[1] LIN Xueyan, ZHANG Cancan, TIAN Minle, TIAN Yongjie. Expression and significance of poly(ADP-ribose) polymerase-1 in endometriosis [J]. Journal of Shandong University (Health Sciences), 2022, 60(2): 27-31.
[2] GENG Chen, YANG Yang, ZHAO Yue, LIU Haoran, CHAO Lan. Identification of differentially expressed genes and Wilms tumor-1 expression in adenomyosis [J]. Journal of Shandong University (Health Sciences), 2021, 59(4): 79-86.
[3] XUE Yuan, LIN Xueyan, XU Ge, TIAN Yongjie. Expression of hypoxia-inducible factor-1α in the serum of patients with endometriosis and its effect on epithelial mesenchymal transition of eutopic endometrial stromal cells [J]. Journal of Shandong University (Health Sciences), 2021, 59(2): 41-47.
[4] LIN Xueyan, LI Chunyan, HOU Xiaoman, TIAN Yongjie. Expressions of PARP-1 and EMT markers in eutopic and ectopic endometrium of adenomyosis [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(9): 36-40.
[5] WU Lukanxuan, ZHU Shan, YU Jinxi, LÜ Chunzi, LI Mingjiang. Expression and significance of programmed death-1 and its ligand PD-L1 in adenomyosis [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(10): 90-96.
[6] FAN Shaohua, ZHANG Yichao, YUAN Xiaodong, BI Jingwen, ZHANG Yichen, LI Yun. Expressions of MiR210 and stat3 following global ischemia in rats and the potential relationship among MiR210, stat3 and HIF-1α [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(3): 1-5.
[7] CHEN Jianhua, ZHU Banghao. Inhibiting Effect of ginsenoside Re on the expression of PARP-1 in human umbilical vein endothelial cell [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(9): 34-38.
[8] LIU Jing, ZHANG Hui, YAN Lei, ZHAO Xing-bo, LI Ming-jiang. Expression and significance of RhoE/Rnd3 protein in adenomyosis [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(5): 116-.
[9] ZHANG Jing-jing1, WANG Zhe1, TIAN Yong-jie1, ZHANG Jie2. Effects of PJ34 on growth activity and cisplatin resistance of ovarian cancer C13* cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(1): 46-50.
[10] . Expressions of PTEN and Akt and relationship to adenomyosis [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(10): 86-90.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] ZHAO Tingting, QI Yana, ZHANG Ying, YUAN Bing, HAN Mingyong. Mouse breast cancer induces changes of the microenvironment in pre-metastatic lung tissue[J]. Journal of Shandong University (Health Sciences), 2022, 60(4): 24 -29 .
[2] CHEN Zhaobo, FANG Min, XUE Haoran, LIU Chunyan. Deubiquitinase USP35 promotes the cells migration and invasion of non-small cell lung cancer[J]. Journal of Shandong University (Health Sciences), 2022, 60(4): 30 -37 .
[3] LI Honghao, YU Jing, CHEN Yali, GUO Shougang. Evaluation of CD4+CD25+FoxP3+ regulatory T cells and FoxP3 mRNA expression in 20 NMOSD patients[J]. Journal of Shandong University (Health Sciences), 2022, 60(4): 50 -54 .
[4] SHAO Na, YIN Hao, LI Yaran, ZHANG Baokun, HUANG Weiwei, LU Shanshan, TANG Jiyou. Study on the mechanism of Suvorexant treatment ameliorates learning and memory impairment in chronic sleep deprivation mice model[J]. Journal of Shandong University (Health Sciences), 2022, 60(4): 17 -23 .
[5] ZHAO Hailong, WANG Hao, FANG Yuqing, MAO Fei, ZHAO Zhangning, TIAN Xiangqi, XU Xinrong, WANG Min, LI Xiuhua. Efficacy of additional idebenone in the treatment of 34 patients with Parkinsons disease with depression[J]. Journal of Shandong University (Health Sciences), 2022, 60(4): 38 -44 .
[6] SHEN Yufei, ZHAO Mei, HU Mi. Help-seeking willingness, help-seeking behaviors and influencing factors in middle school students with suicidal ideation[J]. Journal of Shandong University (Health Sciences), 0, (): 99 -106 .
[7] YUAN Hongtao, JI Congshan, KANG Bing, QIN Songnan, YU Xinxin, GAO Lin, WANG Ximing. Diagnostic value of CT radiomics nomogram for adrenal lipid-poor adenoma and nodular hyperplasia[J]. Journal of Shandong University (Health Sciences), 0, (): 68 -75 .
[8] LIU Liwen, MA Jun, LI Peizheng, ZHANG Xiufang, LIU Yiming. Caregiver burden and influencing factors of 128 patients with Parkinsons disease[J]. Journal of Shandong University (Health Sciences), 2022, 60(4): 45 -49 .
[9] SUN Jiye, WANG Ziou, SUN Xiaowei, LI Hongtao. Effects of traditional Chinese medicine fumigation combined with extracorporeal shock wave therapy on 72 cases of femoroacetabular impingement syndrome and serum inflammatory factor[J]. Journal of Shandong University (Health Sciences), 0, (): 76 -81 .
[10] KONG Xinxin, SUN Shuzhen, LI Qian, CHEN Yuan, ZHOU Aihua, WANG Li, YAO Xiujun. Analysis of 7 cases of anti-H factor antibody-positive hemolytic uremic syndrome[J]. Journal of Shandong University (Health Sciences), 0, (): 82 -86 .