Molecules and Cells

  • 제44권4호
  • /
  • Pages.254-266
  • /
  • 2021
  • /
  • 1016-8478(pISSN)
  • /
  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
권호 표지
DOI QR코드

DOI QR Code

Overexpression of COMP-Angiopoietin-1 in K14-Expressing Cells Impairs Hematopoiesis and Disturbs Erythrocyte Maturation

  • Sim, Hyun-Jaung (Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences and School of Dentistry, Jeonbuk National University) ;
  • Kim, Min-Hye (Department of Bioactive Material Sciences, Research Center of Bioactive Materials, Jeonbuk National University) ;
  • Bhattarai, Govinda (Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences and School of Dentistry, Jeonbuk National University) ;
  • Hwang, Jae-Won (Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences and School of Dentistry, Jeonbuk National University) ;
  • So, Han-Sol (Department of Bioactive Material Sciences, Research Center of Bioactive Materials, Jeonbuk National University) ;
  • Poudel, Sher Bahadur (Department of Basic Science & Craniofacial Biology, College of Dentistry, New York University) ;
  • Cho, Eui-Sic (Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences and School of Dentistry, Jeonbuk National University) ;
  • Kook, Sung-Ho (Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences and School of Dentistry, Jeonbuk National University) ;
  • Lee, Jeong-Chae (Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences and School of Dentistry, Jeonbuk National University)
  • 투고 : 2020.07.19
  • 심사 : 2021.04.05
  • 발행 : 2021.04.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Numerous studies highlight the potential benefits potentials of supplemental cartilage oligomeric matrix protein-angiopoietin-1 (COMP-Ang1) through improved angiogenic effects. However, our recent findings show that excessive overexpression of COMP-Ang1 induces an impaired bone marrow (BM) microenvironment and senescence of hematopoietic stem cells (HSCs). Here, we investigated the underlying mechanisms of how excessive COMP-Ang1 affects the function of BM-conserved stem cells and hematopoiesis using K14-Cre;inducible-COMP-Ang1-transgenic mice. Excessive COMP-Ang1 induced peripheral egression and senescence of BM HSCs and mesenchymal stem cells (MSCs). Excessive COMP-Ang1 also caused abnormal hematopoiesis along with skewed differentiation of HSCs toward myeloid lineage rather than lymphoid lineage. Especially, excessive COMP-Ang1 disturbed late-stage erythroblast maturation, followed by decreased expression of stromal cell-derived factor 1 (SDF-1) and globin transcription factor 1 (GATA-1) and increased levels of superoxide anion and p-p38 kinase. However, transplantation with the mutant-derived BM cells or treatment with rhCOMP-Ang1 protein did not alter the frequency or GATA-1 expression of erythroblasts in recipient mice or in cultured BM cells. Together, our findings suggest that excessive COMP-Ang1 impairs the functions of BM HSCs and MSCs and hematopoietic processes, eventually leading to abnormal erythropoiesis via imbalanced SDF-1/CXCR4 axis and GATA-1 expression rather than Ang1/Tie2 signaling axis alterations.

키워드

과제정보

This research was supported by Basic Science Research Program through the National Research Foundation (NRF) funded by the Ministry of Science, Information and Communications Technology and Future Planning (2018R1A2A3074639, 2019R1A2C2084453, 2020R1C1C1004968, and 2021R1A2C2006032) and by Ministry of Education (2018R1D1A1B07047162), South Korea. We also thank Dr. G.Y. Koh for providing IND-COMP-Ang1-Tg mice and B.-C. Lee for advising in manuscript preparation.

참고문헌

  1. Arai, F., Hirao, A., Ohmura, M., Sato, H., Matsuoka, S., Takubo, K., Lto, K., Koh, G.Y., and Suda, T. (2004). Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 118, 149-161. https://doi.org/10.1016/j.cell.2004.07.004
  2. Bibikova, E., Youn, M.Y., Danilova, N., Yukako, O.U., Yoan, K.G., Ochoa, R., Narla, A., Glader, B., Lin, S., and Sakamoto, K.M. (2014). TNF-mediated inflammation represses GATA1 and activates p38 MAP kinase in RPS19-deficient hematopoietic progenitors. Blood 124, 3791-3798.
  3. Boulais, P. and Frenette, P.S. (2015). Making sense of hematopoietic stem cell niches. Blood 125, 2621-2629. https://doi.org/10.1182/blood-2014-09-570192
  4. Brindle, N.P., Saharinen, P., and Alitalo, K. (2006). Signaling and functions of angiopoietin-1 in vascular protection. Circ. Res. 98, 1014-1023. https://doi.org/10.1161/01.RES.0000218275.54089.12
  5. Chen, J., Kang, J.G., Keyvanfar, K., Young, N.S., and Hwang, P.M. (2016). Long-term adaptation to hypoxia preserves hematopoietic stem cell function. Exp. Hematol. 44, 866-873. https://doi.org/10.1016/j.exphem.2016.04.010
  6. Cho, C.H., Kammerer, R.A., Lee, H.J., Steinmetz, M.O., Ryu, Y.S., Lee, S.H., Yasunaga, K., Kim, K.T., Kim, I., Choi, H.H., et al. (2004). COMP-Ang1: a designed angiopoietin-1 variant with nonleaky angiogenic activity. Proc. Natl. Acad. Sci. U. S. A. 101, 5547-5552. https://doi.org/10.1073/pnas.0307574101
  7. Cho, C.H., Kim, K.E., Byun, J.H., Jang, H.S., Kim, D.K., Baluk, P., Baffert, F., Lee, G.M., Mochizuki, N., Kim, J., et al. (2005). Long-term and sustained COMP-Ang1 induces long-lasting vascular enlargement and enhanced blood flow. Circ. Res. 97, 86-94. https://doi.org/10.1161/01.RES.0000174093.64855.a6
  8. Dassule, H.R., Lewis, P., Bei, M., Maas, R., and McMahon, A.P. (2000). Sonic hedgehog regulates growth and morphogenesis of the tooth. Development 127, 4775-4785. https://doi.org/10.1242/dev.127.22.4775
  9. de Thonel, A., Vandekerckhove, J., Lanneau, D., Selvakumar, S., Courtois, G., Hazoume, A., Brunet, M., Maurel, S., Hammann, A., Ribeil, J.A., et al. (2010). HSP27 controls GATA-1 protein level during erythroid cell differentiation. Blood 116, 85-96.
  10. Ding, L. and Morrison, S.J. (2013). Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches. Nature 495, 231-235. https://doi.org/10.1038/nature11885
  11. Ehninger, A. and Trumpp, A. (2011). The bone marrow stem cell niche grows up: mesenchymal stem cells and macrophages move in. J. Exp. Med. 208, 421-428. https://doi.org/10.1084/jem.20110132
  12. Ferreira, R., Ohneda, K., Yamamoto, M., and Philipsen, S. (2005). GATA1 function, a paradigm for transcription factors in hematopoiesis. Mol. Cell. Biol. 25, 1215-1227. https://doi.org/10.1128/MCB.25.4.1215-1227.2005
  13. Hato, T., Kimura, Y., Morisada, T., Koh, G.Y., Miyata, K., Tabata, M., Kadomatsu, T., Endo, M., Urano, T., Arai, F., et al. (2009). Angiopoietins contribute to lung development by regulating pulmonary vascular network formation. Biochem. Biophys. Res. Commun. 381, 218-223. https://doi.org/10.1016/j.bbrc.2009.02.030
  14. Ikushima, Y.M., Arai, F., Nakamura, Y., Hosokawa, K., Kubota, Y., Hirashima, M., Toyama, H., and Suda, T. (2013). Enhanced Angpt1/Tie2 signaling affects the differentiation and long-term repopulation ability of hematopoietic stem cells. Biochem. Biophys. Res. Commun. 430, 20-25. https://doi.org/10.1016/j.bbrc.2012.11.002
  15. Joo, H.J., Kim, H.S., Park, S.W., Cho, H.J., Kim, H.S., Lim, D.S., Chung, H.M., Kim, I.J., Han, Y.M., and Koh, G.Y. (2011). Angiopoietin-1 promotes endothelial differentiation from embryonic stem cells and induced pluripotent stem cells. Blood 118, 2094-2104. https://doi.org/10.1182/blood.v118.21.2094.2094
  16. Katayama, Y., Battista, M., Kao, W.M., Hidalgo, A., Peired, A.J., Thomas, S.A., and Frenette, P.S. (2006). Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell 124, 407-421. https://doi.org/10.1016/j.cell.2005.10.041
  17. Kertesz, N., Wu, J., Chen, T.H., Sucov, H.M., and Wu, H. (2004). The role of erythropoietin in regulating angiogenesis. Dev. Biol. 276, 101-110. https://doi.org/10.1016/j.ydbio.2004.08.025
  18. Koh, G.Y. (2013). Orchestral actions of angiopoietin-1 in vascular regeneration. Trends Mol. Med. 19, 31-39. https://doi.org/10.1016/j.molmed.2012.10.010
  19. Kook, S.H., Sim, H.J., Hwang, J.W., Baek, Y.H., Kim, C.C., Lee, J.H., Cho, E.S., and Lee, J.C. (2018). Genetic overexpression of COMP-Ang1 impairs BM microenvironment and induces senescence of BM HSCs. Biochem. Biophys. Res. Commun. 499, 669-674. https://doi.org/10.1016/j.bbrc.2018.03.210
  20. Kook, S.H., Yun, C.Y., Sim, H.J., Bhattarai, G., Lee, B.C., Lee, K.Y., Cho, E.S., and Lee, J.C. (2016). Smad4 in osteoblasts exerts a differential impact on HSC fate depending on osteoblast maturation stage. Leukemia 30, 2039-2046. https://doi.org/10.1038/leu.2016.133
  21. Kusumbe, A.P., Ramasamy, S.K., and Adams, R.H. (2014). Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature 507, 323-328. https://doi.org/10.1038/nature13145
  22. Lee, J.Y., Park, D.Y., Park, D.Y., Park, I.T., Chang, W.H., Nakaoka, Y., Komuro, I., Yoo, O.J., and Koh, G.Y. (2014). Angiopoietin-1 suppresses choroidal neovascularization and vascular leakage. Invest. Ophthalmol. Vis. Sci. 55, 2191-2199. https://doi.org/10.1167/iovs.14-13897
  23. Matte, A. and de Franceschi, L. (2019). Oxidation and erythropoiesis. Curr. Opin. Hematol. 26, 145-151. https://doi.org/10.1097/MOH.0000000000000495
  24. Pevny, L., Lin, C.S., D'Agati, V., Simon, M.C., Orkin, S.H., and Costantini, F. (1995). Development of hematopoietic cells lacking transcription factor GATA-1. Development 121, 163-172. https://doi.org/10.1242/dev.121.1.163
  25. Pevny, L., Simon, M.C., Robertson, E., Klein, W.H., Tsai, S.F., D'Agati, V., Orkin, S.H., and Costantini, F. (1991). Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA1. Nature 349, 257-260. https://doi.org/10.1038/349257a0
  26. Soriano, P. (1999). Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat. Genet. 21, 70-71. https://doi.org/10.1038/5007
  27. Suda, T., Takakura, N., and Oike, Y. (2000). Hematopoiesis and angiogenesis. Int. J. Hematol. 71, 99-107.
  28. Sugiyama, T., Kohara, H., Noda, M., and Nagasawa, T. (2006). Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 25, 977-988. https://doi.org/10.1016/j.immuni.2006.10.016
  29. Suri, C., McClain, J., Thurston, G., McDonald, D.M., Zhou, H., Oldmixon, E.H., Sato, T.N., and Yancopoulos, G.D. (1998). Increased vascularization in mice overexpressing angiopoietin-1. Science 282, 468-471. https://doi.org/10.1126/science.282.5388.468
  30. Takakura, N., Watanabe, T., Suenobu, S., Yamada, Y., Noda, T., Ito, Y., Satake, M., and Suda, T. (2000). A role for hematopoietic stem cells in promoting angiogenesis. Cell 102, 199-209. https://doi.org/10.1016/S0092-8674(00)00025-8
  31. Thurston, G., Suri, C., Smith, K., McClain, J., Sato, T.N., Yancopoulos, G.D., and McDonald, D.M. (1999). Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science 286, 2511-2514. https://doi.org/10.1126/science.286.5449.2511
  32. Whyatt, D., Lindeboom, F., Karis, A., Ferreira, R., Milot, E., Hendriks, R., de Bruijn, M., Langeveld, A., Gribnau, J., Grosveld, F., et al. (2000). An intrinsic but cell-nonautonomous defect in GATA-1-overexpressing mouse erythroid cells. Nature 406, 519-524. https://doi.org/10.1038/35020086
  33. Whyatt, D.J., Karis, A., Harkes, I.C., Verkerk, A., Gillemans, N., Elefanty, A.G., Vairo, G., Ploemacher, R., Grosveld, F., and Philipsen, S. (1997). The level of the tissue-specific factor GATA-1 affects the cellcycle machinery. Genes Funct. 1, 11-24. https://doi.org/10.1046/j.1365-4624.1997.00003.x
  34. Youn, S.W., Lee, S.W., Lee, J., Jeong, H.K., Suh, J.W., Yoon, C.H., Kang, H.J., Kim, H.Z., Koh, G.Y., Oh, B.H., et al. (2011). COMP-Ang1 stimulates HIF-1-mediated SDF-1 overexpression and recovers ischemic injury through BM-derived progenitor cell recruitment. Blood 117, 4376-4386. https://doi.org/10.1182/blood-2010-07-295964
  35. Yu, C., Cantor, A.B., Yang, H., Browne, C., Wells, R.A., Fujiwara, Y., and Orkin, S.H. (2002). Targeted deletion of a high-affinity GATA-binding site in the GATA1 promoter leads to selective loss of the eosinophil lineage in vivo. J. Exp. Med. 195, 1387-1395. https://doi.org/10.1084/jem.20020656
  36. Zhang, J., Niu, C., Ye, L., Huang, H., He, X., Tong, W.G., Ross, J., Haug, J., Johnson, T., Feng, J.Q., et al. (2003). Identification of the haematopoietic stem cell niche and control of the niche size. Nature 425, 836-841. https://doi.org/10.1038/nature02041
  37. Zhang, X., Sejas, D.P., Qiu, Y., Williams, D.A., and Pang, Q. (2007). Inflammatory ROS promote and cooperate with the Fanconi anemia mutation for hematopoietic senescence. J. Cell Sci. 120, 1572-1583. https://doi.org/10.1242/jcs.003152
  38. Zhou, B.O., Ding, L., and Morrison, S.J. (2015). Hematopoietic stem and progenitor cells regulate the regeneration of their niche by secreting angiopoietin-1. Elife 4, e05521. https://doi.org/10.7554/eLife.05521
  39. Zhou, Y., He, Y., Xing, W., Zhang, P., Shi, H., Chen, S., Shi, J., Bai, J., Rhodes, S.D., Zhang, F., et al. (2017). An abnormal bone marrow microenviornment contributes to hematopoietic dysfuction in Fanconi anemia. Haematologica 102, 1017-1027. https://doi.org/10.3324/haematol.2016.158717

피인용 문헌

  1. COMP-Ang1: Therapeutic potential of an engineered Angiopoietin-1 variant vol.141, 2021, https://doi.org/10.1016/j.vph.2021.106919