How does signaling pathway works out in human beings?

  • Information transduction between human cells can be achieved through direct contact between adjacent cells, but more importantly, through the secretion of various chemicals by cells to regulate the metabolism and function of themselves and other cells, so in the human body, Information transduction pathways are usually composed of specific cells secreting and releasing information substances (including intercellular and intracellular information substances and carriers, transport pathways, etc.) and target cells (including specific receptors, etc.).

    DO YOU KNOW ANGIOGENESIS SIGNALING PATHWAY?

    Angiogenesis Signaling Pathway is defined as the biological process of the formation of new blood vessels by pre-existing blood vessels. This is a key process that promotes development, skeletal muscle hypertrophy, menstruation, pregnancy and wound healing, and can also lead to angiogenic diseases (such as retinopathy), rheumatoid arthritis, psoriasis, AIDS / Kaposi sarcoma and cancer (tumorigenesis) and other pathological conditions. Angiogenesis is a complex, highly ordered process that relies on endothelial cell (EC).

     

    Vascular endothelial growth factor (VEGF) is a family of proteins required for angiogenesis. VEGF has multiple isotypes, including VEGF-A, VEGF-B, VEGF-C and VEGF-D, each in the embryo. Lymphangiogenesis plays an important role in different angiogenesis environments. VEGF-A is a major angiogenesis mediator. Selective shearing produces four major VEGF-A isoforms of varying lengths (121165189 and 206amino acids), which are paraphoric to heparin sulfate proteins. HSPG has different affinity. The balance between free diffusion and VEGF-A binding to HSPG produces a gradient forming a new tip cell and the endothelial cell that is responsive to angiogenesis signal transduction. The tip cells form the leading edge of the angiogenesis bud, and eventually promote the branches of the blood vessel through the various cell migration steps.

     

    Branching expands first according to site specific metabolic needs and then subdivides into arteries, capillaries, veins and lymphatic vessels, which are composed of Notch-Gridlock, Ephrin-B2/EphB4 and Sonic Hedgehog (SHH) pathway mediated processes. As further vascular maturation and hemodynamic changes occur, endothelial cells (EC) secrete platelet-derived growth factor (PDGF) B, thereby recruiting peridermal cells and VSMC. By expressing angiopoietin 1 (ANG-1), these parietal cells bind to (EC) and induce the activation of TGF- β and the deposition of extracellular matrix (ECM), thus stabilizing the vascular bed. Downstream effectors (including phosphatidylinositol 3 kinase (PI3K), Src) Kinase, (FAK), p38 mitogen-activated protein kinase (p38 MAPK), Smad2/3 and phospholipase C γ (PLC γ) / Erk1/2) can promote endothelial cell survival. The positive and negative transcriptional regulation of these halodromes by microRNA (miRNA) may further affect the neovascularization. In particular, miR-126 has been shown to play an important role in the formation of defective blood vessels and embryo death.

    Pathological and physiological angiogenesis has many similarities in signal transduction activities and changes in cell function and behavior, so it can be used as a new therapeutic option to fight diseases. But one of the key differences is that pathological angiogenesis does not end when tissue perfusion is inadequate. This uncontrolled, cluttered, and unclear growth can hinder the development of new interrupted angiogenesis media.

    Do you know ROS1 Signaling Pathway?
    ROS1 signaling pathway is related to ROS1 gene a lot whose rearrangements were initially identified in human glioma cell lines, followed by ROS1 gene rearrangements in several other malignancies, such as cholangiocarcinoma, ovarian cancer, gastric cancer and non-small cell lung cancer. In non-small cell lung cancer (NSCLC), the mutation frequency is that 1%-2%. ROS1 gene can fuse with multiple genes, and the most important fusion partner is that when CD74,ROS1 is fused with other genes, the kinase domain is generally preserved. The rearrangement of ROS1 leads to continuous activation of kinase, up-regulation of SHP-1, SHP2 and PI3K, AKT, mTOR,MAPK and ERK signaling pathways lead to cell proliferation and tumorigenesis.
    The immunohistochemical detection of ROS1 is simple and easy to operate. However, the requirement of antibody is high, and it is easy to be affected by the background of staining and the standard of interpretation. In short, for fusion mutation of ROS1 gene, it is best to use two or more detection techniques to verify each other, none of which can guarantee 100% promise, but for patients, missed detection is due to all hope.

    Do you know Diabetes Signaling Pathway?

    Many previous studies have shown that genes encoding the transcription factor TCF7L2 in the diabetes signaling pathway are very strong candidate genes for type II diabetes. However, how this factor is involved in the development of type II diabetes has not been well understood. TCF7L2 protein is a key transcriptional effector of Wnt/ β-catenin signaling pathway, and Wnt/ β-catenin signaling pathway can play a very important role in regulating development. Previous studies have shown that this signaling pathway plays a negative role in adipogenesis. But the effects of TCF7L2 on the development and function of adipocytes Nor is it clear.

    In a new study, researchers from the Center for Health Sciences at the University of Texas presented their latest advances in adipocyte development and function in the international academic journal Diabetes. The researchers first found that the expression of TCF7L2 protein increased gradually during the induction and differentiation of 3T3L1 and primary adipocyte precursor cells in vitro, and the expression of TCF7L2 was necessary for the regulation of Wnt signal in adipocyte formation. They then removed HMG-box from the TCF7L2 protein in mature adipocytes of mice DNA binding domain was found to lead to systemic blood glucose intolerance and liver insulin resistance in mice. This phenotype is accompanied by an increase in subcutaneous fat, fat cell hypertrophy, and inflammation.

    Finally, the researchers looked at patients with impaired glucose tolerance and insulin resistance in adipocytes and found a down-regulation of TCF7L2 mRNA expression in adipocytes. These results suggest that TCF7L2 plays a key role in adipose tissue development and function, and this part of the study reveals how TCF7L2 promotes the development of type 2 diabetes.