The recombinant human LIF protein is expressed in mammalian cells. Its expression region spans amino acids 23 to 202 of the full-length mature human LIF protein. It is C-terminally tagged with a 10xHis tag for efficient purification and detection. This recombinant LIF protein is highly pure, with a purity exceeding 95% as determined by SDS-PAGE, and contains less than 1.0 EU/µg endotoxin, as verified by the LAL method. Its biological activity is confirmed through a functional ELISA, where immobilized Human LIF at 2 μg/mL binds to Human LIFR protein (CSB-MP012929HUi9), with an EC50 value between 8.067-9.260 ng/mL.
Human LIF is a cytokine primarily known for its involvement in reproductive biology, particularly in embryo implantation and pregnancy maintenance. Studies have demonstrated that LIF is expressed in the endometrium, with its levels peaking during the implantation window, suggesting its essential role in facilitating the attachment of the blastocyst to the uterine lining [1][2][3]. The interaction of LIF with its receptor LIFR on the surface of the blastocyst is crucial for successful implantation, as both LIF and LIFR are co-expressed during the preimplantation stage [1][2].
Beyond reproductive functions, LIF has been implicated in various other biological processes, including cell differentiation and survival. It has been shown to support the maintenance of stemness in embryonic stem cells, highlighting its importance in developmental biology [4]. In addition, LIF regulates immune responses and inflammation. Elevated levels of LIF have been observed in conditions such as chronic obstructive pulmonary disease (COPD) and certain cancers, indicating its potential role as a biomarker and therapeutic target [5][6]. In colorectal cancer, increased LIF expression correlates with poor prognosis, suggesting its involvement in tumor progression [6].
Moreover, LIF also regulates the hypothalamus-pituitary-adrenal (HPA) axis, influencing adrenal function and steroidogenesis [7]. Its expression in the adrenal cortex underscores its role in the endocrine system, particularly in stress responses and metabolic regulation. Additionally, LIF has been linked to various signaling pathways, including the JAK-STAT pathway, which is critical for mediating its biological effects [8][9].
References:
[1] L. Aghajanova. Leukemia inhibitory factor and human embryo implantation, Annals of the New York Academy of Sciences, vol. 1034, no. 1, p. 176-183, 2004. https://doi.org/10.1196/annals.1335.020
[2] A. Lemons and R. Naz. Birth control vaccine targeting leukemia inhibitory factor, Molecular Reproduction and Development, vol. 79, no. 2, p. 97-106, 2011. https://doi.org/10.1002/mrd.22002
[3] Y. Li, S. Lizhou, D. Zhao, J. Ouyang, & M. Xiang. Aberrant expression of leukemia inhibitory factor receptor (lifr) and leukemia inhibitory factor (lif) is associated with tubal pregnancy occurrence, Turkish Journal of Medical Sciences, vol. 45, p. 214-220, 2015. https://doi.org/10.3906/sag-1307-103
[4] J. Song, B. Koo, S. Chong, K. Kim, D. Choi, T. Vu, et al. Correction: soluble expression of human leukemia inhibitory factor with protein disulfide isomerase in escherichia coli and its simple purification, Plos One, vol. 9, no. 1, 2014. https://doi.org/10.1371/annotation/4b2acdb5-5bab-4bca-8fbc-f9f293b38ee0
[5] J. Poon, M. Campos, R. Foronjy, S. Nath, G. Gupta, C. Railwah, et al. <p>cigarette smoke exposure reduces leukemia inhibitory factor levels during respiratory syncytial viral infection</p>, International Journal of Chronic Obstructive Pulmonary Disease, vol. Volume 14, p. 1305-1315, 2019. https://doi.org/10.2147/copd.s196658
[6] L. Wu, H. Yu, Y. Zhao, C. Zhang, J. Wang, X. Yue, et al. Hif-2α mediates hypoxia-induced lif expression in human colorectal cancer cells, Oncotarget, vol. 6, no. 6, p. 4406-4417, 2015. https://doi.org/10.18632/oncotarget.3017
[7] T. Guran, Ö. Güran, C. Paketçi, O. Kipoğlu, I. Firat, S. Turan, et al. Effects of leukemia inhibitory receptor gene mutations on human hypothalamo–pituitary–adrenal function, Pituitary, vol. 18, no. 4, p. 456-460, 2014. https://doi.org/10.1007/s11102-014-0594-5
[8] D. Chen, Y. Sun, Y. Wei, P. Zhang, A. Rezaeian, J. Teruya‐Feldstein, et al. Lifr is a breast cancer metastasis suppressor upstream of the hippo-yap pathway and a prognostic marker, Nature Medicine, vol. 18, no. 10, p. 1511-1517, 2012. https://doi.org/10.1038/nm.2940
[9] H. Yu, X. Yue, Y. Zhao, X. Li, L. Wu, C. Zhang, et al. Lif negatively regulates tumour-suppressor p53 through stat3/id1/mdm2 in colorectal cancers, Nature Communications, vol. 5, no. 1, 2014. https://doi.org/10.1038/ncomms6218
