DOI QR코드

DOI QR Code

Angiogenic Induction by Trichinella spiralis Infection through Thymosin β4

티모신베타4에의한 선모충(Trichinella spiralis) 감염의 혈관신생 유도 기작

  • Ock, Mee Sun (Department of Parasitology and Gnenetics, Kosin University College of Medicine) ;
  • Cha, Hee-Jae (Department of Parasitology and Gnenetics, Kosin University College of Medicine)
  • 옥미선 (고신대학교 의과대학 기생충학-유전학교실) ;
  • 차희재 (고신대학교 의과대학 기생충학-유전학교실)
  • Received : 2013.08.30
  • Accepted : 2013.09.25
  • Published : 2013.09.30

Abstract

Trichinella spiralis (T. spiralis) has been reported to induce angiogenesis and a supply of nutrients and to act as a reliable waste disposal system by induction of the expression of the angiogenic molecule vascular endothelial cell growth factor (VEGF) during nurse cell formation. However, the mechanism underlying the induction of VEGF in nurse cells by T. spiralis has not yet been defined. Some research has pointed to the possibility of hypoxia in nurse cells, but whether hypoxia occurs in infected muscle or nurse cells has not been studied. It is also a matter of debate whether hypoxia induces the expression of VEGF and subsequent angiogenesis in infected muscle. Recent studies showed that thymosin ${\beta}4$, a potent VEGF-inducing protein, was expressed at a very early stage of muscle infection by T. spiralis, suggesting that VEGF is induced at an early stage in nurse cells. Furthermore, hypoxia was not detected in any nurse cell stage but was detected in inflammatory cells. The findings suggest that induction of angiogenesis by VEGF in T. spiralis-infected nurse cells is mediated by thymosin ${\beta}4$ and unrelated to hypoxia.

Acknowledgement

Supported by : 고신대학교

References

  1. Baldewijns, M. M., van Vlodrop, I. J., Vermeulen, P. B., Soetekouw, P. M., van Engeland, M. and de Bruine, A. P. 2010. VHL and HIF signalling in renal cell carcinogenesis. J Pathol 221, 125-138. https://doi.org/10.1002/path.2689
  2. Baruch, A. M. and Despommier, D. D. 1991. Blood vessels in Trichinella spiralis infections: a study using vascular casts. J Parasitol 77, 99-103. https://doi.org/10.2307/3282565
  3. Capo, V. A., Despommier, D. D. and Polvere, R. I. 1998. Trichinella spiralis: vascular endothelial growth factor is up-regulated within the nurse cell during the early phase of its formation. J Parasitol 84, 209-214. https://doi.org/10.2307/3284472
  4. Cha, H. J., Jeong, M. J. and Kleinman, H. K. 2003. Role of thymosin beta4 in tumor metastasis and angiogenesis. J Natl Cancer Inst 95, 1674-1680. https://doi.org/10.1093/jnci/djg100
  5. Despommier, D., Aron, L. and Turgeon, L. 1975. Trichinella spiralis: growth of the intracellular (muscle) larva. Exp Parasitol 37, 108-116. https://doi.org/10.1016/0014-4894(75)90058-2
  6. Grant, D. S., Rose, W., Yaen, C., Goldstein, A., Martinez, J. and Kleinman, H. 1999. Thymosin beta4 enhances endothelial cell differentiation and angiogenesis. Angiogenesis 3, 125-135. https://doi.org/10.1023/A:1009041911493
  7. Hannappel, E. and Huff, T. 2003. The thymosins. Prothymosin alpha, parathymosin, and beta-thymosins: structure and function. Vitam Horm 66, 257-296. https://doi.org/10.1016/S0083-6729(03)01007-0
  8. Jo, J. O., Kim, S. R., Bae, M. K., Kang, Y. J., Ock, M. S., Kleinman, H. K. and Cha, H. J. 2010. Thymosin beta4 induces the expression of vascular endothelial growth factor (VEGF) in a hypoxia-inducible factor (HIF)-1alpha-dependent manner. Biochim Biophys Acta 1803, 1244-1251. https://doi.org/10.1016/j.bbamcr.2010.07.005
  9. Kang, Y. J., Jo, J. O., Cho, M. K., Yu, H. S., Ock, M. S. and Cha, H. J. 2011. Trichinella spiralis infection induces angiogenic factor thymosin beta4 expression. Vet Parasitol 181, 222-228. https://doi.org/10.1016/j.vetpar.2011.03.058
  10. Kobayashi, T., Okada, F., Fujii, N., Tomita, N., Ito, S., Tazawa, H., Aoyama, T., Choi, S. K., Shibata, T., Fujita, H. and Hosokawa, M. 2002. Thymosin-beta4 regulates motility and metastasis of malignant mouse fibrosarcoma cells. Am J Pathol 160, 869-882. https://doi.org/10.1016/S0002-9440(10)64910-3
  11. Liu, Y. V., Baek, J. H., Zhang, H., Diez, R., Cole, R. N. and Semenza, G. L. 2007. RACK1 competes with HSP90 for binding to HIF-1alpha and is required for O(2)-independent and HSP90 inhibitor-induced degradation of HIF-1alpha. Mol Cell 25, 207-217. https://doi.org/10.1016/j.molcel.2007.01.001
  12. Liu, Y. V. and Semenza, G. L. 2007. RACK1 vs. HSP90: competition for HIF-1 alpha degradation vs. stabilization. Cell Cycle 6, 656-659. https://doi.org/10.4161/cc.6.6.3981
  13. Low, T. L. and Goldstein, A. L. 1982. Chemical characterization of thymosin beta 4. J Biol Chem 257, 1000-1006.
  14. Malinda, K. M., Goldstein, A. L. and Kleinman, H. K. 1997. Thymosin beta 4 stimulates directional migration of human umbilical vein endothelial cells. FASEB J 11, 474-481.
  15. Malinda, K. M., Sidhu, G. S., Mani, H., Banaudha, K., Maheshwari, R. K., Goldstein, A. L. and Kleinman, H. K. 1999. Thymosin beta4 accelerates wound healing. J Invest Dermatol 113, 364-368. https://doi.org/10.1046/j.1523-1747.1999.00708.x
  16. Ock, M. S., Song, K. S., Kleinman, H. and Cha, H. J. 2012. Thymosin beta4 stabilizes hypoxia-inducible factor-1alpha protein in an oxygen-independent manner. Ann N Y Acad Sci 1269, 79-83. https://doi.org/10.1111/j.1749-6632.2012.06657.x
  17. Philp, D., Goldstein, A. L. and Kleinman, H. K. 2004. Thymosin beta4 promotes angiogenesis, wound healing, and hair follicle development. Mech Ageing Dev 125, 113-115. https://doi.org/10.1016/j.mad.2003.11.005
  18. Philp, D., Nguyen, M., Scheremeta, B., St-Surin, S., Villa, A. M., Orgel, A., Kleinman, H. K. and Elkin, M. 2004. Thymosin beta4 increases hair growth by activation of hair follicle stem cells. FASEB J 18, 385-387.
  19. Philp, D., St-Surin, S., Cha, H. J., Moon, H. S., Kleinman, H. K. and Elkin, M. 2007. Thymosin beta 4 induces hair growth via stem cell migration and differentiation. Ann N Y Acad Sci 1112, 95-103. https://doi.org/10.1196/annals.1415.009
  20. Sang, N., Fang, J., Srinivas, V., Leshchinsky, I. and Caro, J. 2002. Carboxyl-terminal transactivation activity of hypoxia- inducible factor 1 alpha is governed by a von Hippel- Lindau protein-independent, hydroxylation-regulated association with p300/CBP. Mol Cell Biol 22, 2984-2992. https://doi.org/10.1128/MCB.22.9.2984-2992.2002
  21. Smart, N., Rossdeutsch, A. and Riley, P. R. 2007. Thymosin beta4 and angiogenesis: modes of action and therapeutic potential. Angiogenesis 10, 229-241. https://doi.org/10.1007/s10456-007-9077-x
  22. Teppema, J. S., Robinson, J. E. and Ruitenberg, E. J. 1973. Ultrastructural aspects of capsule formation in Trichinella spiralis infection in the rat. Parasitology 66, 291-296. https://doi.org/10.1017/S0031182000045224

Cited by

  1. Blood-brain barrier disruption and angiogenesis in a rat model for neurocysticercosis pp.03604012, 2018, https://doi.org/10.1002/jnr.24335