DOI QR코드

DOI QR Code

난소 내 황체조직에서 발정주기별 H-Ras, RLIP76, Angiogenic Receptors mRNA와 Protein의 발현

Expression of H-ras, RLIP76 mRNA and Protein, and Angiogenic Receptors in Corpus Luteum Tissues during Estrous Cycles

  • 김민성 (강원대학교 동물생명과학대학 동물산업융합학과) ;
  • 이상희 (강원대학교 동물자원공동연구소) ;
  • 이승형 (강원대학교 동물생명과학대학 동물산업융합학과)
  • Kim, Minseong (Department of Animal Industry Convergence, College of Animal Life Sciences, Kangwon National University) ;
  • Lee, Sang-Hee (Institute of Animal Resources, Kangwon National University) ;
  • Lee, Seunghyung (Department of Animal Industry Convergence, College of Animal Life Sciences, Kangwon National University)
  • 투고 : 2018.09.20
  • 심사 : 2018.10.25
  • 발행 : 2018.12.31

초록

황체는 발정주기에 따라 형성과 퇴행이 반복되는 일시적인 내분비기관이다. 본 연구에서는 황체와 종양의 혈관신생과정이 기능적과 구조적 기전이 유사하다는 가정하에 실시하였다. 먼저, 우리는 혈관신생관련 수용체인 VEGFR2와 Tie 2 mRNA와 단백질 발현을 검토하였다. 또한, RLIP76와 H-ras의 발현도 측정하였다. 그 결과, 초기와 중기황체에서 VEGFR2와 Tie 2 mRNA와 단백질의 발현되었으나, 후기황체에서는 발현이 감소하였다. H-ras의 경우, mRMA와 단백질 모두 초기와 중기황체에서 발현되었으나, 후기황체에서는 발현되지 않았다. RLIP76 mRNA은 모든 황체주기에서 발현되었고, 단백질은 초기황체에서 강하게 발현되었다. 이상의 결과를 토대로, RLIP76와 H-ras는 황체의 기능에 관여하고, 황체의 혈관신생과정 메커니즘에 중요한 역할을 할 것이다.

Corpus luteum (CL) is a transient endocrinal tissue that undergoes repeated formation and regression during the estrous cycle. In this study, we hypothesized that the functional and structural mechanism of angiogenesis is similar between CL and tumor formation. First, we measured mRNA and protein expression of angiogenic receptors (vascular endothelial growth factor receptor-2, VEGFR2; Tie 2) in the early, middle, and late phase CL tissues during the estrous cycle. Ral-interacting protein of 76 kDa (RLIP76) and H-ras mRNA and protein were also expressed in the CL tissues. VEGFR2 and Tie 2 mRNA and protein were expressed in the early and middle phase CLs and decreased in the late phase. H-ras mRNA and protein were expressed in the early and middle phase CLs, but not in the late phase. RLIP76 mRNA was expressed in all phase CLs, and the protein expression was highest in early phase CLs. We suggest that RLIP76 and H-ras, an oncogenic gene, regulate the function of the CL during the estrous cycle, and the proteins will play an important role in the angiogenic mechanism of the CL.

키워드

참고문헌

  1. Chouhan V, Dangi S, Gupta M, Babitha V, Khan F, Panda R, et al. Stimulatory effect of vascular endothelial growth factor on progesterone production and survivability of cultured bubaline luteal cells. Anim Reprod Sci. 2014;148:251-259. https://doi.org/10.1016/j.anireprosci.2014.06.009
  2. Tomac J, Cekinovic D, Arapovic J. Biology of the corpus luteum. Periodicum biologorum. 2011;113:43-49.
  3. Schams D, Berisha B. Regulation of corpus luteum function in cattle-an overview. Reprod Domest Anim. 2004;39:241-251. https://doi.org/10.1111/j.1439-0531.2004.00509.x
  4. Berisha B, Schams D, Rodler D, Pfaffl MW. Angiogenesis in the ovary-the most important regulatory event for follicle and corpus luteum development and function in cow-An overview. Anat Histol Embryol. 2016;45:124-130. https://doi.org/10.1111/ahe.12180
  5. Abulafia O, Sherer DM. Angiogenesis of the ovary. Am J Obstet Gynecol. 2000;182:240-246. https://doi.org/10.1016/S0002-9378(00)70519-9
  6. Benyo DF, Pate JL. Tumor necrosis factor-alpha alters bovine luteal cell synthetic capacity and viability. Endocrinology. 1992;130:854-860.
  7. Tamanini C, De Ambrogi M. Angiogenesis in developing follicle and corpus luteum. Reprod Domest Anim. 2004;39:206-216. https://doi.org/10.1111/j.1439-0531.2004.00505.x
  8. Risau W. Mechanisms of angiogenesis. Nature. 1997;386:671. https://doi.org/10.1038/386671a0
  9. Berisha B, Schams D. Ovarian function in ruminants. Domest Anim Endocrinol. 2005;29:305-317. https://doi.org/10.1016/j.domaniend.2005.02.035
  10. Lee S, Goldfinger LE. RLIP76 regulates HIF-1 activity, VEGF expression and secretion in tumor cells, and secretome transactivation of endothelial cells. FASEB J. 2014;28:4158-4168. https://doi.org/10.1096/fj.14-255711
  11. Awasthi YC, Singhal SS, Gupta S, Ahmad H, Zimniak P, Radominska A, et al. Purification and characterization of an ATPase from human liver which catalyzes ATP hydrolysis in the presence of the conjugates of bilirubin, bile acids and glutathione. Biochem Biophys Res Commun. 1991;175:1090-1096. https://doi.org/10.1016/0006-291X(91)91677-5
  12. Lee S, Wurtzel JG, Singhal SS, Awasthi S, Goldfinger LE. RALBP1/RLIP76 depletion in mice suppresses tumor growth by inhibiting tumor neovascularization. Cancer Res. 2012;72:5165-5173. https://doi.org/ 10.1158/0008-5472.CAN-12-0468.
  13. Singhal SS, Singhal J, Yadav S, Dwivedi S, Boor PJ, Awasthi YC, et al. Regression of lung and colon cancer xenografts by depleting or inhibiting RLIP76 (Ral-binding protein 1). Cancer Res. 2007;67:4382-4389. https://doi.org/10.1158/0008-5472.CAN-06-4124
  14. Singhal SS, Awasthi YC, Awasthi S. Regression of melanoma in a murine model by RLIP76 depletion. Cancer Res. 2006;66:2354-2360. https://doi.org/10.1158/0008-5472.CAN-05-3534
  15. Lee S, Lee SH, Yang BK, Park CK. The expression of VEGF, myoglobin and CRP2 proteins regulating endometrial remodeling in the porcine endometrial tissues during follicular and luteal phase. Animal Sci J. 2017;88:1291-1297. https://doi.org/10.1111/asj.12774
  16. Smith MW, Stevenson JS. Fate of the dominant follicle, embryonal survival, and pregnancy rates in dairy cattle treated with prostaglandin $F2{\alpha}$ and progestins in the absence or presence of a functional corpus luteum. J Anim Sci. 1995;73:3743-3751. https://doi.org/10.2527/1995.73123743x
  17. Farin C, Moeller C, Mayan H, Gamboni F, Sawyer H, Niswender G. Effect of luteinizing hormone and human chorionic gonadotropin on cell populations in the ovine corpus luteum. Biol Reprod. 1988;38:413-421. https://doi.org/10.1095/biolreprod38.2.413
  18. Garcia MR. Leptin contributes to the development of the corpus luteum. Cell Dev Biol. 2017;6:190. https://doi.org/10.4172/2168-9296.1000190.
  19. de Carvalho Sousa LMM, Mendes GP, Campos DB, Baruselli PS, de Carvalho Papa P. Equine chorionic gonadotropin modulates the expression of genes related to the structure and function of the bovine corpus luteum. PLoS One. 2016;11:e0164089. https://doi.org/10.1371/journal.pone.0164089
  20. Wiles JR, Katchko RA, Benavides EA, O'Gorman CW, Escudero JM, Keisler DH, et al. The effect of leptin on luteal angiogenic factors during the luteal phase of the estrous cycle in goats. Anim Reprod Sci. 2014;148:121-129. https://doi.org/10.1016/j.anireprosci.2014.05.002
  21. Stirling D, Magness R, Stone R, Waterman M, Simpson E. Angiotensin II inhibits luteinizing hormone-stimulated cholesterol side chain cleavage expression and stimulates basic fibroblast growth factor expression in bovine luteal cells in primary culture. J Biol Chem. 1990;265:5-8.
  22. Robinson RS, Woad KJ, Hammond AJ, Laird M, Hunter MG, Mann GE. Angiogenesis and vascular function in the ovary. Reproduction. 2009;138:869-881. https://doi.org/10.1530/REP-09-0283
  23. Chouhan V, Panda R, Yadav V, Babitha V, Khan F, Das G, et al. Expression and localization of vascular endothelial growth factor and its receptors in the corpus luteum during oestrous cycle in water buffaloes (Bubalus bubalis). Reprod Domest Anim. 2013;48:810-818. https://doi.org/10.1111/rda.12168
  24. Schams D, Berisha B. Angiogenic factors in the bovine corpus luteum. J Reprod Dev. 2002;48:233-242. https://doi.org/10.1262/jrd.48.233
  25. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997;277:55-60. https://doi.org/10.1126/science.277.5322.55
  26. Mishra S, Parmar M, Yadav V, Reshma R, Bharati J, Bharti M, et al. Expression and localization of angiopoietin family in corpus luteum during different stages of oestrous cycle and modulatory role of angiopoietins on steroidogenesis, angiogenesis and survivability of cultured buffalo luteal cells. Reprod Domest Anim. 2016;51:855-869. https://doi.org/10.1111/rda.12739
  27. Buratta S, Urbanelli L, Sagini K, Giovagnoli S, Caponi S, Fioretto D, et al. Extracellular vesicles released by fibroblasts undergoing H-Ras induced senescence show changes in lipid profile. PLoS One. 2017;12:e0188840. https://doi.org/10.1371/journal.pone.0188840
  28. Arbiser JL, Moses MA, Fernandez CA, Ghiso N, Cao Y, Klauber N, et al. Oncogenic H-ras stimulates tumor angiogenesis by two distinct pathways. Proc Natl Acad Sci U S A. 1997;94:861-866. https://doi.org/10.1073/pnas.94.3.861