Recombinant human Placenta Growth Factor (PGF) protein (amino acids 19-170) is produced by inserting the PGF gene fragment into a plasmid, transforming E. coli cells, and purifying the expressed protein via affinity chromatography. SDS-PAGE analysis confirms a purity exceeding 97%. Bioactivity is validated by its chemoattractive effect on human monocytes at concentrations ranging from 5.0-50 ng/ml. Endotoxin levels are below 1.0 EU/µg, as determined by the LAL method.
Human PGF, a member of the VEGF family, plays a crucial role in angiogenesis and vasculogenesis, particularly during pregnancy. Primarily secreted by the placental syncytiotrophoblast, it promotes blood vessel formation essential for proper placental and fetal development [1, 2]. Alternative splicing of its mRNA generates multiple isoforms with varying structures and functions [2].
PGF interacts with receptors including VEGFR-1, influencing endothelial cells and regulating placental blood flow [3, 4]. Its expression is modulated by factors such as hypoxia, increasing PGF levels in response to fluctuating oxygen levels during pregnancy [5]. Furthermore, PGF is implicated in the pathophysiology of pregnancy complications, such as preeclampsia, often exhibiting an imbalanced ratio with sFlt-1 (soluble fms-like tyrosine kinase-1) [5, 4].
PGF also participates in placental immune regulation, modulating maternal immune responses to maintain a healthy pregnancy and prevent fetal rejection [6]. Its presence in the placental secretome suggests its potential as a biomarker for pregnancy complications, as altered levels may indicate placental dysfunction [7, 8].
References:
[1] Koh, P., Won, C., Noh, H., Cho, G., & Choi, W. (2005). Expression of pituitary adenylate cyclase activating polypeptide and its type I receptor mRNAs in human placenta. Journal of Veterinary Science, 6(1), 1. https://doi.org/10.4142/jvs.2005.6.1.1
[2] Lacal, P., Failla, C., et al. (2000). Human melanoma cells secrete and respond to placenta growth factor and vascular endothelial growth factor. Journal of Investigative Dermatology, 115(6), 1000-1007. https://doi.org/10.1046/j.1523-1747.2000.00199.x
[3] Murakami, Y., Kobayashi, T., et al. (2005). Exogenous vascular endothelial growth factor can induce preeclampsia-like symptoms in pregnant mice. Seminars in Thrombosis and Hemostasis, 31(3), 307-313. https://doi.org/10.1055/s-2005-872437
[4] Grimaldi, B., Kohan-Ghadr, H., & Drewlo, S. (2022). The potential for placental activation of PPARγ to improve the angiogenic profile in preeclampsia. Cells, 11(21), 3514. https://doi.org/10.3390/cells11213514
[5] Colson, A., Depoix, C., Baldin, P., Hubinont, C., Sonveaux, P., & Debiève, F. (2020). Hypoxia-inducible factor 2α impairs human cytotrophoblast syncytialization: new insights into placental dysfunction and fetal growth restriction. The FASEB Journal, 34(11), 15222-15235. https://doi.org/10.1096/fj.202001681r
[6] Hsiao, E., & Patterson, P. (2011). Activation of the maternal immune system induces endocrine changes in the placenta via IL-6. Brain Behavior and Immunity, 25(4), 604-615. https://doi.org/10.1016/j.bbi.2010.12.017
[7] Napso, T., Zhao, X., et al. (2020). Unbiased placental secretome characterization identifies candidates for pregnancy complications. https://doi.org/10.1101/2020.07.12.198366
[8] Michelsen, T., Henriksen, T., Reinhold, D., Powell, T., & Jansson, T. (2018). The human placental proteome secreted into the maternal and fetal circulations in normal pregnancy based on 4-vessel sampling. The FASEB Journal, 33(2), 2944-2956. https://doi.org/10.1096/fj.201801193r
Cytokines are small proteins that play crucial roles in cell signaling. They are produced by a broad range of cells, including immune cells like macrophages, B lymphocytes, T lymphocytes, and mast cells, as well as endothelial cells, fibroblasts, and various stromal cells. Cytokines can be classified into several categories based on their functions and structures, including interleukins (ILs), interferons (IFNs), tumor necrosis factors (TNFs), chemokines, and growth factors.
Key Biological Properties: Cytokines are characterized by their ability to modulate the balance between humoral and cell-based immune responses, and they regulate the maturation, growth, and responsiveness of particular cell populations.
Expression Patterns: Cytokine expression is highly regulated and can be transient or sustained depending on the physiological or pathological context. They are typically produced in response to an immune stimulus.
Tissue Distribution: Cytokines are distributed throughout the body and can act locally or systemically. They are found in various tissues, including blood, lymphoid organs, and sites of inflammation.
Primary Biological Functions: Cytokines are involved in a wide range of biological processes, including cell proliferation, differentiation, and apoptosis. They play a pivotal role in immune responses, inflammation, and hematopoiesis.
Role in Immune Responses: Cytokines are essential for the development and functioning of both the innate and adaptive immune systems. They help in the activation and recruitment of immune cells to infection sites and facilitate communication between immune cells.
Pathogen Recognition: Cytokines are involved in the recognition and elimination of pathogens. They enhance the ability of immune cells to detect and respond to microbial infections.
Mechanisms with Other Molecules and Cells: Cytokines exert their effects by binding to specific receptors on the surface of target cells. This binding triggers intracellular signaling pathways that lead to changes in gene expression and cellular behavior.
Binding Partners: Cytokines interact with a variety of binding partners, including receptors, co-receptors, and other signaling molecules. These interactions are crucial for the specificity and diversity of cytokine actions.
Downstream Signaling Cascades: Upon binding to their receptors, cytokines activate downstream signaling cascades such as the JAK-STAT pathway, MAPK pathway, and NF-κB pathway. These pathways mediate the cellular responses to cytokines.
Regulatory Mechanisms: The expression and activity of cytokines are tightly regulated at multiple levels, including transcriptional regulation, mRNA stability, and post-translational modifications.
Transcriptional Regulation: Cytokine gene expression is controlled by various transcription factors that respond to extracellular signals. These factors bind to promoter regions of cytokine genes and modulate their transcription.
Post-Translational Modifications: Cytokines undergo several post-translational modifications, such as glycosylation and phosphorylation, which can affect their stability, activity, and interactions with receptors.
Biomedical Research: Cytokines are extensively studied in biomedical research for their roles in health and disease. They are used as biomarkers for disease diagnosis and prognosis.
Diagnostic Tools: Cytokines are used in diagnostic assays to detect and monitor immune responses and inflammatory conditions. They can serve as indicators of disease activity and therapeutic response.
Therapeutic Strategies: Cytokines are used as therapeutic agents in the treatment of various diseases, including cancer, autoimmune disorders, and infectious diseases. They can be administered as recombinant proteins or targeted by specific inhibitors.
Development: Cytokines play critical roles in embryonic development and the maturation of the immune system. They are involved in the differentiation and proliferation of various cell types.
Aging: The production and activity of cytokines change with age, contributing to the aging process and age-related diseases. Dysregulation of cytokine signaling is associated with chronic inflammation and immune senescence.
Disease: Cytokines are implicated in the pathogenesis of numerous diseases, including inflammatory and autoimmune disorders, infections, and cancers. They can act as mediators of disease progression and targets for therapeutic intervention.