Interaction of the transforming growth factor-β and Notch signaling pathways in the regulation of granulosa cell proliferation
Xiao-Feng Sun A B , Xing-Hong Sun A C , Shun-Feng Cheng A C , Jun-Jie Wang A C , Yan-Ni Feng A C , Yong Zhao A C , Shen Yin A C , Zhu-Mei Hou A D , Wei Shen A C and Xi-Feng Zhang E F
+ Author Affiliations
- Author Affiliations
A Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao 266109, China.
B College of Life Science, Qingdao Agricultural University, Qingdao 266109, China.
C College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, China.
D College of Marine Science and Engineering, Qingdao Agricultural University, Qingdao 266109, China.
E College of Biological and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan 430023, China.
F Corresponding author. Email: zhangxf9465@163.com
Reproduction, Fertility and Development 28(12) 1873-1881 https://doi.org/10.1071/RD14398
Submitted: 21 October 2014 Accepted: 6 May 2015 Published: 3 June 2015
Abstract
The Notch and transforming growth factor (TGF)-β signalling pathways play an important role in granulosa cell proliferation. However, the mechanisms underlying the cross-talk between these two signalling pathways are unknown. Herein we demonstrated a functional synergism between Notch and TGF-β signalling in the regulation of preantral granulosa cell (PAGC) proliferation. Activation of TGF-β signalling increased hairy/enhancer-of-split related with YRPW motif 2 gene (Hey2) expression (one of the target genes of the Notch pathway) in PAGCs, and suppression of TGF-β signalling by Smad3 knockdown reduced Hey2 expression. Inhibition of the proliferation of PAGCs by N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butylester (DAPT), an inhibitor of Notch signalling, was rescued by both the addition of ActA and overexpression of Smad3, indicating an interaction between the TGF-β and Notch signalling pathways. Co-immunoprecipitation (CoIP) and chromatin immunoprecipitation (ChIP) assays were performed to identify the point of interaction between the two signalling pathways. CoIP showed direct protein–protein interaction between Smad3 and Notch2 intracellular domain (NICD2), whereas ChIP showed that Smad3 could be recruited to the promoter regions of Notch target genes as a transcription factor. Therefore, the findings of the present study support the idea that nuclear Smad3 protein can integrate with NICD2 to form a complex that acts as a transcription factor to bind specific DNA motifs in Notch target genes, such as Hey1 and Hey2, and thus participates in the transcriptional regulation of Notch target genes, as well as regulation of the proliferation of PAGCs.
Additional keywords: activin A, cross-talk.
References
Amarir, S., Marx, M., and Calothy, G. (2010). Notch signaling activation suppresses v-Src-induced transformation of neural cells by restoring TGF-β-mediated differentiation. PLoS One 5, e13572.| Notch signaling activation suppresses v-Src-induced transformation of neural cells by restoring TGF-β-mediated differentiation.Crossref | GoogleScholarGoogle Scholar | 21042581PubMed |
Andrieux, G., Le Borgne, M., and Théret, N. (2014). An integrative modeling ramework reveals plasticity of TGF-β signaling. BMC Syst. Biol. 8, 30.
| An integrative modeling ramework reveals plasticity of TGF-β signaling.Crossref | GoogleScholarGoogle Scholar | 24618419PubMed |
Artavanis-Tsakonas, S., Rand, M. D., and Lake, R. J. (1999). Notch signaling: cell fate control and signal integration in development. Science 284, 770–776.
| Notch signaling: cell fate control and signal integration in development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXivVKrs7Y%3D&md5=02b38a2d20e08d1d22734ca9cc6f6ffcCAS | 10221902PubMed |
Attisano, L., and Wrana, J. L. (2002). Signal transduction by the TGF-superfamily. Science 296, 1646–1647.
| Signal transduction by the TGF-superfamily.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XktlCht7k%3D&md5=845ba400a4b3995a4a0cfd878f00c9a6CAS | 12040180PubMed |
Blokzijl, A., Dahlqvist, C., Reissmann, E., Falk, A., Moliner, A., Dahlqvist, C., Lendahl, U., and Ibáñez, C. F. (2003). Cross-talk between the Notch and TGF-β signaling pathways mediated by interaction of the Notch intracellular domain with Smad3. J. Cell Biol. 163, 723–728.
| Cross-talk between the Notch and TGF-β signaling pathways mediated by interaction of the Notch intracellular domain with Smad3.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXpsVCltro%3D&md5=fb4dfc9fdfd39b3e92754c7f20b045d9CAS | 14638857PubMed |
Bray, S. J. (2006). Notch signalling: a simple pathway becomes complex. Nat. Rev. Mol. Cell Biol. 7, 678–689.
| Notch signalling: a simple pathway becomes complex.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xot12isr4%3D&md5=b26777887d8829db306260b459d492a4CAS | 16921404PubMed |
Chen, C. L., Fu, X. F., Wang, L. Q., Wang, J. J., Ma, H. G., Cheng, S. F., Hou, Z. M., Ma, J. M., Quan, G. B., Shen, W., and Li, L. (2014). Primordial follicle assembly was regulated by Notch signaling pathway in the mice. Mol. Biol. Rep. 41, 1891–1899.
| Primordial follicle assembly was regulated by Notch signaling pathway in the mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXotFOmug%3D%3D&md5=8223540b19f36fafc84be006453dcf80CAS | 24430295PubMed |
Choi, J. H., Park, J. T., Davidson, B., Morin, P. J., Shih, IeM., and Wang, T. L. (2008). Jagged-1 and Notch3 juxtacrine loop regulates ovarian tumor growth and adhesion. Cancer Res. 68, 5716–5723.
| Jagged-1 and Notch3 juxtacrine loop regulates ovarian tumor growth and adhesion.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXovVCns70%3D&md5=fe664e74dabd9516f879bbcd593972c5CAS | 18632624PubMed |
Chu, P. C., Chuang, H. C., Kulp, S. K., and Chen, C. S. (2012). The mRNA-stabilizing factor HuR protein is targeted by β-TrCP protein for degradation in response to glycolysis inhibition. J. Biol. Chem. 287, 43 639–43 650.
| The mRNA-stabilizing factor HuR protein is targeted by β-TrCP protein for degradation in response to glycolysis inhibition.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhvVOrt7rO&md5=28cab6481839d58e13e415fe9b787f7bCAS |
Derynck, R., and Zhang, Y. E. (2003). Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 425, 577–584.
| Smad-dependent and Smad-independent pathways in TGF-beta family signalling.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXnvV2hs7c%3D&md5=122ac40fbbbe643f4734f3a07b1c5cf2CAS | 14534577PubMed |
Feng, Y. M., Liang, G. J., Pan, B., Qin, X. S., Zhang, X. F., Chen, C. L., Li, L., Cheng, S. F., De Felici, M., and Shen, W. (2014). Notch pathway regulates female germ cell meiosis progression and early oogenesis events in fetal mouse. Cell Cycle 13, 782–791.
| Notch pathway regulates female germ cell meiosis progression and early oogenesis events in fetal mouse.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhtFOht7fL&md5=9e374a9abe94ec13e318a8251526f7daCAS | 24398584PubMed |
Heldin, C. H., Miyazono, K., and ten Dijke, P. (1997). TGF-β signaling from cell membrane to nucleus through SMAD proteins. Nature 390, 465–471.
| TGF-β signaling from cell membrane to nucleus through SMAD proteins.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXnvFyrtLo%3D&md5=d992d3e41548957bf3fa4b7fce93df23CAS | 9393997PubMed |
Hopfer, O., Zwahlen, D., Fey, M. F., and Aebi, S. (2005). The Notch pathway in ovarian carcinomas and adenomas. Br. J. Cancer 93, 709–718.
| The Notch pathway in ovarian carcinomas and adenomas.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtV2kt73K&md5=de37fd90549bf0b366b9af0ab135961bCAS | 16136053PubMed |
Johnson, J., Espinoza, T., McGaughey, R. W., Rawls, A., and Wilson-Rawls, J. (2001). Notch pathway genes are expressed in mammalian ovarian follicles. Mech. Dev. 109, 355–361.
| Notch pathway genes are expressed in mammalian ovarian follicles.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXos1KgtLY%3D&md5=e9a5591d4d403e3d951034e891c49ba0CAS | 11731249PubMed |
Jovanovic, V. P., Sauer, C. M., Shawber, C. J., Gomez, R., Wang, X., Sauer, M. V., Kitajewski, J., and Zimmermann, R. C. (2013). Intraovarian regulation of gonadotropin-dependent folliculogenesis depends on notch receptor signaling pathways not involving Delta-like ligand 4 (Dll4). Reprod. Biol. Endocrinol. 11, 43.
| Intraovarian regulation of gonadotropin-dependent folliculogenesis depends on notch receptor signaling pathways not involving Delta-like ligand 4 (Dll4).Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXptlyjsbc%3D&md5=e66c2c968d63d4761b64d8510d64e028CAS | 23675950PubMed |
Kovall, R. A. (2008). More complicated than it looks: assembly of Notch pathway transcription complexes. Oncogene 27, 5099–5109.
| More complicated than it looks: assembly of Notch pathway transcription complexes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtVGgtLbF&md5=9040b7eafc20b6568741d94c69c338b1CAS | 18758478PubMed |
Li, Y., Cheng, S. Y., Chen, N., and Reith, M. E. A. (2010). Interrelation of dopamine transporter oligomerization and surface presence as studied with mutant transporter proteins and amphetamine. J. Neurochem. 114, 873–885.
| Interrelation of dopamine transporter oligomerization and surface presence as studied with mutant transporter proteins and amphetamine.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXpslygurg%3D&md5=78190ccad1be036770826b07ee8f343dCAS | 20492355PubMed |
Logeat, F., Bessia, C., Brou, C., LeBail, O., Jarriault, S., Seidah, N. G., and Israël, A. (1998). The Notch1 receptor is cleaved constitutively by a furin-like convertase. Proc. Natl Acad. Sci. USA 95, 8108–8112.
| The Notch1 receptor is cleaved constitutively by a furin-like convertase.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXks1SktbY%3D&md5=9dc75ecdd96e60a2fd7fdf5115aa312dCAS | 9653148PubMed |
Massagué, J., Blain, S. W., and Lo, R. S. (2000). TGF-β signaling in growth control, cancer, and heritable disorders. Cell 103, 295–309.
| TGF-β signaling in growth control, cancer, and heritable disorders.Crossref | GoogleScholarGoogle Scholar | 11057902PubMed |
Nomura, M., Sakamoto, R., Morinaga, H., Wang, L., Mukasa, C., and Takayanaqi, R. (2013). Activin stimulates CYP19A gene expression in human ovarian granulosa cell-like KGN cells via the Smad2 signaling pathway. Biochem. Biophys. Res. Commun. 436, 443–448.
| Activin stimulates CYP19A gene expression in human ovarian granulosa cell-like KGN cells via the Smad2 signaling pathway.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhtVWgsbvM&md5=215e3417a8354f7893bbccd9f3b8fcceCAS | 23747729PubMed |
Rabinovici, J., Spencer, S. J., Doldi, N., Goldsmith, P. C., Schwall, R., and Jaffe, R. B. (1992). Activin-A as an intraovarian modulator: actions, localization, and regulation of the intact dimer in human ovarian cells. J. Clin. Invest. 89, 1528–1536.
| Activin-A as an intraovarian modulator: actions, localization, and regulation of the intact dimer in human ovarian cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK38XisVyrsLk%3D&md5=fa10b9143b302aa6e9569bb1baaa6c8dCAS | 1569191PubMed |
Roberts, A. B., and Sporn, M. B. (1990). The transforming growth factors-β. In ‘Handbook of Experimental Pharmacology. Peptide Growth Factors and Their Receptors’. (Eds MB Sporn and AB Roberts.) pp. 419–472. (Springer: Berlin.)
Rognoni, E., Widmaier, M., Jakobson, M., Ruppert, R., Ussar, S., Katsougkri, D., Böttcher, R. T., Lai-Cheong, J. E., Rifkin, D. B., McGrath, J. A., and Fässler, R. (2014). Kindlin-1 controls Wnt and TGF-β availability to regulate cutaneous stem cell proliferation. Nat. Med. 20, 350–359.
| Kindlin-1 controls Wnt and TGF-β availability to regulate cutaneous stem cell proliferation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXltFKlu7k%3D&md5=4d19a447c5c33add81763ffd9e3b2adbCAS | 24681597PubMed |
Sjölund, J., Boström, A. K., Lindgren, D., Manna, S., Moustakas, A., Ljungberg, B., Johansson, M., Fredlund, E., and Axelson, H. (2011). The Notch and TGF-β signaling pathways contribute to the aggressiveness of clear cell renal cell carcinoma. PLoS One 6, e23057.
| The Notch and TGF-β signaling pathways contribute to the aggressiveness of clear cell renal cell carcinoma.Crossref | GoogleScholarGoogle Scholar | 21826227PubMed |
Trombly, D. J., Woodruff, T. K., and Mayo, K. E. (2009). Suppression of Notch signaling in the neonatal mouse ovary decreases primordial follicle formation. Endocrinology 150, 1014–1024.
| Suppression of Notch signaling in the neonatal mouse ovary decreases primordial follicle formation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhs1Sgt74%3D&md5=7c79769be72bec93bbb3b9fefdce696fCAS | 18818300PubMed |
Vale, W., Rivier, J., Vauqhan, J., McClintock, R., Corrigan, A., Woo, W., Karr, D., and Spiess, J. (1986). Purification and characterization of an FSH releasing protein from porcine ovarian follicular fluid. Nature 321, 776–779.
| Purification and characterization of an FSH releasing protein from porcine ovarian follicular fluid.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL28XltVyktbk%3D&md5=319781788de8053584a4d0db802e0430CAS | 3012369PubMed |
Xu, J., and Gridley, T. (2013). Notch2 is required in somatic cells for breakdown of ovarian germ-cell nests and formation of primordial follicles. BMC Biol. 11, 13.
| Notch2 is required in somatic cells for breakdown of ovarian germ-cell nests and formation of primordial follicles.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXnsFajtb4%3D&md5=27a408ed39ea5f142de467067a92dc09CAS | 23406467PubMed |
Yao, G., Yin, M., Lian, J., Tian, H., Liu, L., Li, X., and Sun, F. (2010). MicroRNA-224 is involved in transforming growth factor-beta-mediated mouse granulosa cell proliferation and granulosa cell function by targeting Smad4. Mol. Endocrinol. 24, 540–551.
| MicroRNA-224 is involved in transforming growth factor-beta-mediated mouse granulosa cell proliferation and granulosa cell function by targeting Smad4.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXjt1ehsrw%3D&md5=781f823c918e1a88a2495aa9e80746bcCAS | 20118412PubMed |
Zavadil, J., Bitzer, M., Liang, D., Yang, Y. C., Massimi, A., Kneitz, S., Piek, E., and Bottinger, E. P. (2001). Genetic programs of epithelial cell plasticity directed by transforming growth factor-β. Proc. Natl Acad. Sci. USA 98, 6686–6691.
| Genetic programs of epithelial cell plasticity directed by transforming growth factor-β.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXksVOkur4%3D&md5=44100de370f147cbe733bfbfcf742e0aCAS | 11390996PubMed |
Zavadil, J., Cermak, L., Soto-Nieves, N., and Böttinger, E. (2004). Integration of TGF-β/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition. EMBO J. 23, 1155–1165.
| Integration of TGF-β/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhvFChurw%3D&md5=831d19f8764ac7e61a7217dcc4a76876CAS | 14976548PubMed |
Zhang, C. P., Yang, J. L., Zhang, J., Li, L., Huang, L., Ji, S. Y., Hu, Z. Y., Gao, F., and Liu, Y. X. (2011). Notch signaling is involved in ovarian follicle development by regulating granulosa cell proliferation. Endocrinology 152, 2437–2447.
| Notch signaling is involved in ovarian follicle development by regulating granulosa cell proliferation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXns1Sntb4%3D&md5=c6e088270e7f6903421c47b9e757b105CAS | 21427220PubMed |
Zhang, Z. P., Liang, G. J., Zhang, X. F., Zhang, G. L., Chao, H. H., Li, L., Sun, X. F., Min, L. J., Pan, Q. J., Shi, Q. H., Sun, Q. Y., De Felici, M., and Shen, W. (2012). Growth of mouse oocytes to maturity from premeiotic germ cells in vitro. PLoS One 7, e41771.
| Growth of mouse oocytes to maturity from premeiotic germ cells in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtFWisbjM&md5=075b9e2ee0ccb8f7cca87229c1f1309cCAS | 22848595PubMed |
