干細胞的旁分泌機制已被認為是促進梗死區心肌再生、修復損傷心肌細胞的主要途徑。隨著進一步的深入研究,發現分泌型卷曲相關蛋白2 (secreted frizzled-related protein 2,Sfrp 2)與干細胞的旁分泌機制有著密切的聯系,它通過競爭結合Wnt信號通路的特異性卷曲受體(Fz),從而抑制Wnt通路的信號傳導,調控細胞的凋亡、分化等生命過程,成為近年來研究的熱點。我們就Sfrp 2通過Wnt信號途徑參與調節干細胞治療心肌梗死的機制作一綜述。
引用本文: 路喆鑫,連鋒. 分泌型卷曲相關蛋白2在心肌再生治療中的作用. 中國胸心血管外科臨床雜志, 2012, 19(4): 423-426. doi: 復制
1. | Osteoarthritis Cartilage, 2009, 17 (7):933-943. |
2. | Mirotsou M,Zhang Z,Deb A,et al. Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair. Proc Natl Acad Sci U S A,2007,104 (5):1643-1648. |
3. | 張偉,賀光照,馬兵. 分泌型凋亡相關蛋白1的研究進展. 中華內分泌外科雜志,2011,5 (1):63-64,67.. |
4. | Rochais F, Mesbah K, Kelly RG. Signaling pathways controlling second heart field development. Circ Res, 2009, 104 (8):933-942. |
5. | Katoh M. WNT and FGF gene clusters (review). Int J Oncol,2002,21 (6):1269-1273. |
6. | Yang F,Zeng Q,Yu G,et al. Wnt/beta-catenin signaling inhibits death receptor-mediated apoptosis and promotes invasive growth of HNSCC. Cell Signal,2006,18 (5):679-687. |
7. | Cai J,Mutoh N,Shin JO,et al. Wnt5a plays a crucial role in determining tooth size during murine tooth development. Cell Tissue Res,2011, 345 (3):367-377. |
8. | Sokol SY. Maintaining embryonic stem cell pluripotency with Wnt signaling. Development, 2011, 138 (20):4341-4350. |
9. | Katoh M, Katoh M. WNT signaling pathway and stem cell signaling network. Clin Cancer Res, 2007, 13(14) :4042-4045. |
10. | Price MC. CKI, there’s more than one:casein kinase I family members in Wnt and Hedgehog signaling. Genes, 2006, 20 (4) :399-410. |
11. | Gao C, Chen YG. Dishevelled:the hub of Wnt signaling. Cell Signal, 2010, 22 (5):717-727. |
12. | Joeng KS, Schumacher CA, Zylstra-Diegel CR, et al. Lrp5 and Lrp6 redundantly control skeletal development in the mouse embryo. Dev Biol, 2011, 359 (2):222-229. |
13. | Minami Y, Oishi I, Endo M, et al. Ror-family receptor tyrosine kinases in noncanonical Wnt signaling:their implications in developmental morphogenesis and human diseases. Dev Dyn, 2010, 239 (1):1-15. |
14. | Lu XW, Borchers AM, Jolicoeur C, et al. PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates. Nature, 2004, 430 (6995):93-98. |
15. | Barker N. The canonical Wnt/beta-catenin signalling pathway. Methods Mol Biol, 2008, 468:5-15. |
16. | Nelson WJ, Nusse R. Convergence of Wnt, beta-catenin, and cadherin pathways. Science, 2004,303 (5663):1483-1487. |
17. | Gordon MD, Nusse R. Wnt signaling:Multiple pathways, multiple receptors, and multiple transcription factors. J Biol Chem, 2006, 281 (32):22429-22433. |
18. | Weng LH, Wang CJ, Ko JY, et al. Inflammation induction of Dickkopf-1 mediates chondrocyte apoptosis in osteoarthritic joint. |
19. | Li Q, Wang X, Wu X, et al. Daxx cooperates with the Axin/HIPK2/p53 complex to induce cell death. Cancer Res, 2007, 67 (1):66-74. |
20. | Zhang Z, Deb A, Zhang Z, et al. Secreted frizzled related protein 2 protects cells from apoptosis by blocking the effect of canonical Wnt3a. J Mol Cell Cardiol, 2009, 46 (3):370-377. |
21. | Cselenyi CS, Lee E. Context-dependent activation or inhibition of Wnt-beta-catenin signaling by Kremen. Sci Signal, 2008, 1 (8):pe10. |
22. | Nilsson LM, Sun ZW, Nilsson J, et al. Novel blocker of NFAT activation inhibits IL-6 production in human myometrial arteries and reduces vascular smooth muscle cell proliferation. Am J Physiol Cell Physiol, 2007, 292 (3):C1167-C1178. |
23. | Sugimura R, Li L. Noncanonical Wnt signaling in vertebrate development, stem cells, and diseases. Birth Defects Res C Embryo Today, 2010, 90 (4):243-256. |
24. | Takashi M, Keiko H, Miura M, et al. Vascular endothelial growth factor- and thrombin-induced termination factor, down syndrome critical region-1, attenuates endothelial cell proliferation and angiogenesis. J Biol Chem, 2004, 279 (48):50537-50554. |
25. | Zaichuk TA, Shroff EH, Emmanuel R, et al. Nuclear factor of activated T cells balances angiogenesis activation and inhibition. J Exp Med, 2004, 199 (11):1513-1522. |
26. | Howard S, Deroo T, Fujita Y, et al. A positive role of cadherin in Wnt/β-catenin signalling during epithelial-mesenchymal transition. PLoS One, 2011, 6 (8):e23899. |
27. | Courtwright A, Siamakpour-Reihani S, Arbiser JL, et al. Secreted frizzle-related protein 2 stimulates angiogenesis via a calcineurin/NFAT signaling pathway. Cancer Res, 2009, 69 (11):4621-4628. |
28. | Alfaro MP, Vincent A, Saraswati S, et al. sFRP2 suppression of bone morphogenic protein (BMP) and Wnt signaling mediates mesenchymal stem cell (MSC) self-renewal promoting engraftment and myocardial repair. J Biol Chem, 2010, 285 (46):35645-35653. |
29. | Manton KJ, Leong DF, Cool SM, et al. Disruption of heparan and chondroitin sulfate signaling enhances mesenchymal stem cell-derived osteogenic differentiation via bone morphogenetic protein signaling pathways. Stem Cells, 2007, 25 (11):2845-2854. |
30. | Gaur T, Rich L, Lengner CJ, et al. Secreted frizzled related protein 1 regulates Wnt signaling for BMP2 induced chondrocyte differentiation. J Cell Physiol, 2006, 208 (1):87-96. |
31. | Goldring MB, Tsuchimochi K, Ijiri K. The control of chondrogenesis. J Cell Biochem, 2006, 97 (1):33-44. |
32. | Kobayashi K, Luo M, Zhang Y, et al. Secreted frizzled-related protein 2 is a procollagen C proteinase enhancer with a role in fibrosis associated with myocardial infarction. Nat Cell Biol, 2009, 11 (1):46-55. |
33. | He W,Zhang L,Ni A,et al. Exogenously administered secreted frizzled related protein 2 (Sfrp2) reduces fibrosis and improves cardiac function in a rat model of myocardial infarction. Proc Natl Acad Sci U S A,2010,107(49):21110-21115. |
- 1. Osteoarthritis Cartilage, 2009, 17 (7):933-943.
- 2. Mirotsou M,Zhang Z,Deb A,et al. Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair. Proc Natl Acad Sci U S A,2007,104 (5):1643-1648.
- 3. 張偉,賀光照,馬兵. 分泌型凋亡相關蛋白1的研究進展. 中華內分泌外科雜志,2011,5 (1):63-64,67..
- 4. Rochais F, Mesbah K, Kelly RG. Signaling pathways controlling second heart field development. Circ Res, 2009, 104 (8):933-942.
- 5. Katoh M. WNT and FGF gene clusters (review). Int J Oncol,2002,21 (6):1269-1273.
- 6. Yang F,Zeng Q,Yu G,et al. Wnt/beta-catenin signaling inhibits death receptor-mediated apoptosis and promotes invasive growth of HNSCC. Cell Signal,2006,18 (5):679-687.
- 7. Cai J,Mutoh N,Shin JO,et al. Wnt5a plays a crucial role in determining tooth size during murine tooth development. Cell Tissue Res,2011, 345 (3):367-377.
- 8. Sokol SY. Maintaining embryonic stem cell pluripotency with Wnt signaling. Development, 2011, 138 (20):4341-4350.
- 9. Katoh M, Katoh M. WNT signaling pathway and stem cell signaling network. Clin Cancer Res, 2007, 13(14) :4042-4045.
- 10. Price MC. CKI, there’s more than one:casein kinase I family members in Wnt and Hedgehog signaling. Genes, 2006, 20 (4) :399-410.
- 11. Gao C, Chen YG. Dishevelled:the hub of Wnt signaling. Cell Signal, 2010, 22 (5):717-727.
- 12. Joeng KS, Schumacher CA, Zylstra-Diegel CR, et al. Lrp5 and Lrp6 redundantly control skeletal development in the mouse embryo. Dev Biol, 2011, 359 (2):222-229.
- 13. Minami Y, Oishi I, Endo M, et al. Ror-family receptor tyrosine kinases in noncanonical Wnt signaling:their implications in developmental morphogenesis and human diseases. Dev Dyn, 2010, 239 (1):1-15.
- 14. Lu XW, Borchers AM, Jolicoeur C, et al. PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates. Nature, 2004, 430 (6995):93-98.
- 15. Barker N. The canonical Wnt/beta-catenin signalling pathway. Methods Mol Biol, 2008, 468:5-15.
- 16. Nelson WJ, Nusse R. Convergence of Wnt, beta-catenin, and cadherin pathways. Science, 2004,303 (5663):1483-1487.
- 17. Gordon MD, Nusse R. Wnt signaling:Multiple pathways, multiple receptors, and multiple transcription factors. J Biol Chem, 2006, 281 (32):22429-22433.
- 18. Weng LH, Wang CJ, Ko JY, et al. Inflammation induction of Dickkopf-1 mediates chondrocyte apoptosis in osteoarthritic joint.
- 19. Li Q, Wang X, Wu X, et al. Daxx cooperates with the Axin/HIPK2/p53 complex to induce cell death. Cancer Res, 2007, 67 (1):66-74.
- 20. Zhang Z, Deb A, Zhang Z, et al. Secreted frizzled related protein 2 protects cells from apoptosis by blocking the effect of canonical Wnt3a. J Mol Cell Cardiol, 2009, 46 (3):370-377.
- 21. Cselenyi CS, Lee E. Context-dependent activation or inhibition of Wnt-beta-catenin signaling by Kremen. Sci Signal, 2008, 1 (8):pe10.
- 22. Nilsson LM, Sun ZW, Nilsson J, et al. Novel blocker of NFAT activation inhibits IL-6 production in human myometrial arteries and reduces vascular smooth muscle cell proliferation. Am J Physiol Cell Physiol, 2007, 292 (3):C1167-C1178.
- 23. Sugimura R, Li L. Noncanonical Wnt signaling in vertebrate development, stem cells, and diseases. Birth Defects Res C Embryo Today, 2010, 90 (4):243-256.
- 24. Takashi M, Keiko H, Miura M, et al. Vascular endothelial growth factor- and thrombin-induced termination factor, down syndrome critical region-1, attenuates endothelial cell proliferation and angiogenesis. J Biol Chem, 2004, 279 (48):50537-50554.
- 25. Zaichuk TA, Shroff EH, Emmanuel R, et al. Nuclear factor of activated T cells balances angiogenesis activation and inhibition. J Exp Med, 2004, 199 (11):1513-1522.
- 26. Howard S, Deroo T, Fujita Y, et al. A positive role of cadherin in Wnt/β-catenin signalling during epithelial-mesenchymal transition. PLoS One, 2011, 6 (8):e23899.
- 27. Courtwright A, Siamakpour-Reihani S, Arbiser JL, et al. Secreted frizzle-related protein 2 stimulates angiogenesis via a calcineurin/NFAT signaling pathway. Cancer Res, 2009, 69 (11):4621-4628.
- 28. Alfaro MP, Vincent A, Saraswati S, et al. sFRP2 suppression of bone morphogenic protein (BMP) and Wnt signaling mediates mesenchymal stem cell (MSC) self-renewal promoting engraftment and myocardial repair. J Biol Chem, 2010, 285 (46):35645-35653.
- 29. Manton KJ, Leong DF, Cool SM, et al. Disruption of heparan and chondroitin sulfate signaling enhances mesenchymal stem cell-derived osteogenic differentiation via bone morphogenetic protein signaling pathways. Stem Cells, 2007, 25 (11):2845-2854.
- 30. Gaur T, Rich L, Lengner CJ, et al. Secreted frizzled related protein 1 regulates Wnt signaling for BMP2 induced chondrocyte differentiation. J Cell Physiol, 2006, 208 (1):87-96.
- 31. Goldring MB, Tsuchimochi K, Ijiri K. The control of chondrogenesis. J Cell Biochem, 2006, 97 (1):33-44.
- 32. Kobayashi K, Luo M, Zhang Y, et al. Secreted frizzled-related protein 2 is a procollagen C proteinase enhancer with a role in fibrosis associated with myocardial infarction. Nat Cell Biol, 2009, 11 (1):46-55.
- 33. He W,Zhang L,Ni A,et al. Exogenously administered secreted frizzled related protein 2 (Sfrp2) reduces fibrosis and improves cardiac function in a rat model of myocardial infarction. Proc Natl Acad Sci U S A,2010,107(49):21110-21115.