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Effects of Angelicae Gigantis Radix on Gene Expression of Ovarian Tissue in Polycystic Ovary Syndrome Rats

당귀(當歸)가 다낭성난소증후군이 유발된 흰쥐 난소조직의 유전자 발현에 미치는 영향

  • Ryu, Ki-Jun (Dept. of OB&GY, College of Oriental Medicine, Dong-Shin University) ;
  • Cho, Sung-Hee (Dept. of OB&GY, College of Oriental Medicine, Dong-Shin University)
  • 류기준 (동신대학교 한의과대학 부인과 교실) ;
  • 조성희 (동신대학교 한의과대학 부인과 교실)
  • Received : 2011.07.28
  • Accepted : 2011.08.08
  • Published : 2011.08.31

Abstract

Objectives: This study was performed to investigate the effects of Angelicae gigantis Radix (AGR) which is one of the most useful herbal-drug to treat patients with Polycystic Ovary Syndrome (PCOS) in Oriental medicine on gene expression of ovary tissue. Methods: The effects of AGR on gene expression of ovary tissue resected from PCOS induced rats using single injection of $\ss$-Estradiol 17-valerate (EV) was measured using microarray technique, and the functional analysis on these genes was conducted. Results: Total 2,812 genes were up-regulated or down-regulated, 1,421 genes were up-regulated, 1,391 genes were down-regulated by induction of PCOS. Up-regulated genes were mainly involved in biological function such as cell signalling pathways and inflammatory response. Expression levels of 1,442 genes were restored to those of naive animals by administration of AGR. 558 genes were restored to those of naive animals, which were lowered by induction of PCOS. 884 genes were lowered to naive levels, which were elevated by induction of PCOS. The functions of restored genes were partially involved in the restoration of expression levels, which were changed by induction of PCOS. Especially, up-regulated gene by induction of PCOS were mainly involved in these changes. These results mean restorative effects of AGR on damaged functions by induction of PCOS. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as IRS2, MCM10, ORC2L related in up-regulated genes, CTBP2, CD44, RHOA, related in down-regulated genes that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: Restored genes by AGR were thought to have common pathways related in regulation of gene expressions. Especially, genes in restored expression levels by AGR, which were up-regulated by induction of PCOS, were regulated by 9 of common transcription factors, genes in restored expression levels by AGR, which were down-regulated by induction of PCOS, were involved in 25 of common transcription factors.

Keywords

References

  1. 대한산부인과학회. 부인과학. 서울:고려의학. 2007:362-71.
  2. 한의부인과학 교재편찬위원회. 한의부인과학. 서울:도서출판 정담. 2002:135-6.
  3. 김동일, 윤종원, 이태균. 다낭성난소증후군의 문헌적고찰. 대한한방부인과학회지. 1997;10(1):73-91.
  4. Pak SC et al. Effect of Korean red ginseng extract in a steroid-induced polycystic ovary murine model. Arch Pharm Res. 2009;32(3):347-52. https://doi.org/10.1007/s12272-009-1306-y
  5. 양승정 등. 蒼附導痰湯이 Estradiol Valerate로 유발된 백서의 다낭성 난소에 미치는 영향. 대한한방부인과학회지. 2002;15(2):1-11.
  6. 권세라 등. 三陰交. 子宮穴 전침 자극이 백서의 다낭성 난소에 미치는 영향. 대한한방부인과학회지. 2003;16(2):76-86.
  7. 유영기 등. 腎氣丸合蒼附導痰湯이 Estradiol Valerate로 유도된 흰쥐의 다낭성 난소에 미치는 영향. 대한한방부인과학회지. 2007;20(1):84-98.
  8. 남은정 등. 定經湯이 Estradiol Valerate로 유도된 흰쥐의 다낭성 난소에 미치는 영향. 대한한방부인과학회지. 2007;20(1):99-113.
  9. 이연경 등. 歸脾湯이 Estradiol Valerate로 유도된 흰쥐의 다낭성 난소에 미치는 영향. 대한한방부인과학회지. 2008;21(3):60-74.
  10. 김희주, 김윤상, 임은미. 蒼附六君湯이 estradiol valerate로 유도된 흰쥐의 다낭성 난소에 미치는 영향. 大韓韓方婦人科學會誌. 2008;21(2):1-16.
  11. 양동선. 香附子가 estradiol valerate로 유발된 백서의 다낭성 난소에 미치는 影響. 동신대학교 대학원 학위논문. 2010.
  12. 구희준. 皂角刺가 estradiol valerate로 유발된 백서의 다낭성 난소에 미치는 影響. 동신대학교 대학원 학위논문. 2010.
  13. 전국한의과대학본초학교실. 본초학. 서울:영림사. 2000:578-80.
  14. 江蘇新醫學院編. 中藥大辭典. 上海:上海科學技術出版社. 1977:102-9.
  15. Caillol M et al. Pituitary and ovarian responses to luteinizing-hormone-releasing hormone during pregnancy and after parturition in brown hares (Lepus europaeus). J Reprod Fertil. 1991;92(1):89-97. https://doi.org/10.1530/jrf.0.0920089
  16. Florell SR et al. Preservation of RNA for functional genomic studies: a multidisciplinary tumor bank protocol. Mod Pathol. 2001;14(2):116-28. https://doi.org/10.1038/modpathol.3880267
  17. Weis S et al. Quality control for microarray analysis of human brain samples: The impact of postmortem factors, RNA characteristics, and histopathology. J Neurosci Methods. 2007 Sep 30;165(2):198-209. https://doi.org/10.1016/j.jneumeth.2007.06.001
  18. Zahurak M et al. Pre-processing Agilent microarray data. BMC Bioinformatics. 2007;8:142. https://doi.org/10.1186/1471-2105-8-142
  19. Pavlicek A, Hrda S, Flegr J. Free-Tree-freeware program for construction of phylogenetic trees on the basis of distance data and bootstrap/jackknife analysis of the tree robustness. Application in the RAPD analysis of genus Frenkelia. Folia Biol(Praha). 1999;45(3):97-9.
  20. Khatri P et al. Onto-Tools: new additions and improvements in 2006. Nucleic Acids Res. 2007;35:W206-11. https://doi.org/10.1093/nar/gkm327
  21. Tarca AL et al. A novel signaling pathway impact analysis. Bioinformatics. 2009;25(1):75-82. https://doi.org/10.1093/bioinformatics/btn577
  22. Shannon P et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498-504. https://doi.org/10.1101/gr.1239303
  23. Tonon L, Touzet H, Varre JS. TFM-Explorer: mining cis-regulatory regions in genomes. Nucleic Acids Res. 2010;38 Suppl:W286-92. https://doi.org/10.1093/nar/gkq473
  24. Stein IF. Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. AM Jobstet Gynecol. 1935;29:181-91. https://doi.org/10.1016/S0002-9378(15)30642-6
  25. Barbieri RL et al. The role of hyperinsulinemia in the pathogenesis of ovarian hyperandrogenism. Fertil Steril. 1988;50:197-212. https://doi.org/10.1016/S0015-0282(16)60060-2
  26. Franks S. Polycystic ovary syndrome: a changing perspecti. Clinical Endocrinology. 1989;31:87-120. https://doi.org/10.1111/j.1365-2265.1989.tb00457.x
  27. Zawadzki JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A et al.. editors. Polycystic Ovary Syndrome. 3rd ed. Boston: Blackwell Scientific Publications. 1992;377-84.
  28. 노정현. 다낭성 난소 증후군의 진단과 치료. 대한내분비학회 연수강좌. 2007:58-66.
  29. 김동일, 윤종원, 이태균. 다낭성 난소 증후군에 관한 문헌적 고찰. 대한한방부인과학회지. 1997;10(1):73-91.
  30. 윤소영, 강명자. 다낭성 난소 증후군 환자의 한방 치료에 대한 임상적 고찰. 대한한방부인과학회지. 2000;13(2):437-51.
  31. 주병주 등. 當歸芍藥散이 실험적으로 유발된 흰쥐의 자궁내막증의 발달 및 관련 cytokine에 미치는 영향. 대한한방부인과학회지. 2008;21(4):104-27.
  32. 김미진 등. 寒冷증상과 冷帶下를 겸한 여고생 월경통에 대한 酒煮當歸丸의 효능에 관한 임상적 연구. 대한한방체열학회지. 2005;4(1):1-14.
  33. 문덕빈 등. 여고생 월경통에 대한 酒煮當歸丸의 효능에 관한 임상적 연구. 대한한방부인과학회지. 2005;18(2):83-99.
  34. 유동렬. 임신유지에 활용되는 金櫃當歸散에 대한 연구. 대한한방부인과학회지. 1998;11(2):135-64.
  35. 권용주, 정진홍, 유동렬. 加味當歸散煎湯液이 임신마우스의 면역세포에 미치는 영향. 대한한방부인과학회지. 1999;11(1):91-108.
  36. 신용완 등. 加味當歸散을 투여한 임신병 환자 7例에 대한 임상보고. 대한한방부인과학회지. 2003;16(4):180-8.
  37. 신선미 등. 자궁경부무력증 환자 1例에 대한 임상보고. 대한한방부인과학회지. 2007;20(2):196-204.
  38. 김상철, 이휘재, 김병수. 마이크로어레이 자료의 사전 처리 순서에 따른 검색의 일치도 분석. 응용통계연구. 2009;22(3):585-94.
  39. 김병수 등. cDNA 마이크로어레이에서 유전자간 상관 관계에 대한 보고. 응용통계연구. 2009;22(3):617-26.
  40. 이종훈 등. cDNA microarray를 이용한 위선암에서의 유전자 발현에 관한 연구. 대한소화기학회지. 2003;42(6):484-95.
  41. Kimizuka F, Kato I. DNA chip technologies and their applications: towards functional genomics. Tanpakushitsu Kakusan Koso. 1998;43(13):2004-11.
  42. Sokol DL et al. Real time detection of DNA.RNA hybridization in living cells. Proc Natl Acad Sci USA. 1998;95(20):11538-43. https://doi.org/10.1073/pnas.95.20.11538
  43. 배윤위 등. 단일가닥 DNA를 이용한 암세포 성장 억제 유전자 발굴. 한국미생물생명공학회지. 2010;38(1):70-6.
  44. Paddison PJ et al. A resource for large-scale RNA-interference-based screens in mammals. Nature. 2004;428(6981):427-31. https://doi.org/10.1038/nature02370
  45. Ogihara T et al. 14-3-3 protein binds to insulin receptor substrate-1, one of the binding sites of which is in the phosphotyrosine binding domain. J Biol Chem. 1997;272(40):25267-74. https://doi.org/10.1074/jbc.272.40.25267
  46. Izumi M et al. The human homolog of Saccharomyces cerevisiae Mcm10 interacts with replication factors and dissociates from nuclease-resistant nuclear structures in G(2) phase. Nucleic Acids Res. 2000;28(23):4769-77. https://doi.org/10.1093/nar/28.23.4769
  47. Takahara K et al.. Mouse and human homologues of the yeast origin of replication recognition complex subunit ORC2 and chromosomal localization of the cognate human gene ORC2L. Genomics. 1996;31(1):119-22. https://doi.org/10.1006/geno.1996.0018
  48. Katsanis N, Fisher EM. A novel C-terminal binding protein(CTBP2) is closely related to CTBP1, an adenovirus E1A-binding protein, and maps to human chromosome 21q21.3. Genomics. 1998;47(2):294-9. https://doi.org/10.1006/geno.1997.5115
  49. Griffith JS et al. Menstrual endometrial cells from women with endometriosis demonstrate increased adherence to peritoneal cells and increased expression of CD44 splice variants. Fertil. Steril. 2010;93(6):1745-9. https://doi.org/10.1016/j.fertnstert.2008.12.012
  50. Yiu G, He Z. Glial inhibition of CNS axon regeneration. Nat. Rev. Neurosci. 2006;7(8):617-27. https://doi.org/10.1038/nrn1956

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