Abstract
The cellular repressor of E1A-stimulated genes (CREG) is a secreted glycoprotein that inhibits cell proliferation and/or enhances differentiation. CREG is widely expressed in adult tissues such as the brain, heart, lungs, liver, intestines and kidneys in mice. We investigated the level of CREG expression during mouse embryogenesis and its distribution at 18.5 days post coitus (dpc) using immunohistochemical staining with diaminobenzidine, western blotting and reverse transcription-polymerase chain reaction. CREG expression was first detected in mouse embryos at 4.5 dpc. It was expressed at almost all stages up to 18.5 dpc. The level of CREG was found to increase gradually and was highest at 18.5 dpc. Western blotting showed that the CREG protein was expressed at higher levels in the brain, heart, intestines and kidneys than in the lungs and liver at 18.5 dpc. In 9.5 dpc embryos, CREG was expressed only in the endothelial cells of blood vessels, after the vascular lumen had formed. With advanced differentiation, vascular smooth muscle cells developed in the embryonic vascular structures; the expression of smooth muscle α-actin protein and CREG were positive and increased gradually in 10.5 dpc embryonic vessels. CREG expression in the embryonic blood vessels peaked at 15.5 dpc and was reduced slightly at 18.5 dpc. These results indicate that CREG is expressed during mouse embryogenesis and might participate in the differentiation of these organs during embryogenesis.
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References
Journet A, Chapel A, Kieffer S, Louwagie M, Luche S, Garin J (2000) Towards a human repertoire of monocytic lysosomal proteins. Electrophoresis 21(16):3411–3419
Veal E, Eisenstein M, Tseng ZH, Gill G (1998) A cellular repressor of E1A-stimulated genes that inhibits activation by E2F. Mol Cell Biol 18(9):5032–5041
Veal E, Groisman R, Eisenstein M, Gill G (2000) The secreted glycoprotein CREG enhances differentiation of NTERA-2 human embryonal carcinoma cells. Oncogene 19(17):2120–2128
Slansky JE, Farnham PJ (1996) Introduction to the E2F family: protein structure and gene regulation. Curr Top Microbiol 208:1–30
Sacher M, Di Bacco A, Lunin VV, Ye Z, Wagner J, Gill G, Cygler M (2005) The crystal structure of CREG, a secreted glycoprotein involved in cellular growth and differentiation. Proc Natl Acad Sci USA 102(51):18326–18331
Di Bacco A, Gill G (2003) The secreted glycoprotein CREG inhibits cell growth dependent on the mannose-6-phosphate/insulin-like growth factor II receptor. Oncogene 22(35):5436–5445
Xu L, Liu JM, Chen LY (2004) CREG, a new regulator of ERK1/2 in cardiac hypertrophy. J Hypertens 22(8):1579–1587
Gordon PV, Paxton JB, Fox NS (2005) The cellular repressor of E1A-stimulated genes mediates glucocorticoid-induced loss of the type-2 IGF receptor in ileal epithelial cells. J Endocrinol 185(2):265–273
Han YL, Guo P, Sun M, Guo L, Luan B, Kang J, Yan C, Li S (2008) Secreted CREG inhibits cell proliferation mediated by mannose 6-phosphate/insulin-like growth factor II receptor in NIH3T3 fibroblasts. Genes cells 13(9):977–986
Han YL, Xu HM, Deng J, Hu Y, Kang J, Liu HW, Yan CH (2006) Over-expression of the cellular repressor of E1A-stimulated genes inhibits the apoptosis of human vascular smooth muscle cells in vitro. Sheng Li Xue Bao 58(4):324–330
Han Y, Deng J, Guo L, Yan C, Liang M, Kang J, Liu H, Graham AM, Li S (2008) CREG promotes a mature smooth muscle cell phenotype and reduces neointimal formation in balloon-injured rat carotid artery. Cardiovasc Res 78(3):597–604
Han Y, Guo L, Yan C, Guo P, Deng J, Mai X, Kang J, Li S (2008) Adenovirus-mediated intra-arterial delivery of cellular repressor of E1A-stimulated genes inhibits neointima formation in rabbits after balloon injury. J Vasc Surg 48(1):201–209
Chen ZL, Momota Y, Kato K, Taniguchi M, Inoue N, Shiosaka S, Yoshida S (1998) Expression of neuropsin mRNA in the mouse embryo and the pregnant uterus. J Histochem Cytochem 46(3):313–320
Cai H, Hu J, Song P, Gong W (2006) PSM2, a novel protein similar to MCAF2, is involved in the mouse embryonic and adult male gonad development. Mol Biol Rep 33(3):159–166
Zhang Q, Lin G, Gu Y, Peng J, Nie Z, Huang Y, Lu G (2009) Borealin is differentially expressed in ES cells and is essential for the early development of embryonic cells. Mol Biol Rep 36(3):603–609
Li W, Yu ZX, Kotin RM (2005) Profiles of PrKX expression in developmental mouse embryo and human tissues. J Histochem Cytochem 53(8):1003–1009
Sengupta A, Sridaran R (2008) Expression and localization of gonadotropin-releasing hormone receptor in the rat oviduct during pregnancy. J Histochem Cytochem 56(1):25–31
Olson EN, Srivastava D (1996) Molecular pathways controlling heart development. Science 272(5262):671–676
Fishman Chien KR MC, Chien KR (1997) Fashioning the vertebrate heart: earliest embryonic decisions. Development 124(11):2099–2117
Schmid P, Cox D, Bilbe G, Maier R, McMaster GK (1991) Differential expression of TGF beta 1, beta 2 and beta 3 genes during mouse embryogenesis. Development 111(1):117–130
Schmid Schulz WA P, Schulz WA (1990) Coexpression of the c-myc protooncogene with alpha-fetoprotein and albumin in fetal mouse liver. Differentiation 45(2):96–102
Schmid P, Lorenz A, Hameister H, Montenarh M (1991) Expression of p53 during mouse embryogenesis. Development 113(3):857–865
Sorokin L, Ekblom P (1992) Development of tubular and glomerular cells of the kidney. Kidney Int 41(3):657–664
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Yang, G., Han, Y., Tian, X. et al. Pattern of expression of the CREG gene and CREG protein in the mouse embryo. Mol Biol Rep 38, 2133–2140 (2011). https://doi.org/10.1007/s11033-010-0340-7
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DOI: https://doi.org/10.1007/s11033-010-0340-7