ATX converts lysophosphatidylcholine into LPA. They act on specific GPCRs. It has been observed to activate multiple signaling pathways (figure 3). The outcome of LPA signaling depends on the innate LPA receptor (co-)expression patterns and tissue context. The cellular responses of LPA include stimulation of cell migration, survival and in the proliferation process. Abnormal ATX and LPA signaling are the root causes of many conditions in the body. Ischemia and hypoxia plays an integral role in causing damage to cardiac myocytes during myocardialinfarction. LPA protects many kinds of cell types from hypoxia-induced apoptosis.
These include cardiac myocytes, renalcells and mesenchymal stem cells to name a few (24-25). Experiments showed that LPAR1 and LPAR3 contribute to hypertrophic response. It executed through activation of Gi and multiple downstream effectors. These include Rho, PI3K/Akt, and NF-kB. It is observed in vivo and in vitro (26, 27). LPA suppresses is oprenaline induced the cell shortening. It enables by the activation of LPA1 or LPA3 in a PTX sensitive action. Lipoprotein lipase (LPL) activity is also increased by LPA in cardiacmyocytes, then incraing the utilization and in the deposition of lipids. These subsequently lead to contractility impairment (28). Many studies seem to suggest that significant contribution of genetic or biological factors is found in the psychiatric disorders. LPA aids to the progression of some of the psychiatric diseases, such as schizophrenia and bipolar disorders, even though it has the potential to alter the physiology of neurons, glial cells and their related progenitors (29). LPA also aids to the progression of tumors and cancers. The first report of LPA which can induce in vitro tumor cell invasion was documented in 1993 (30). Subsequent research analysis indicates that LPA is the causal variables for many of the tumor progressions in the body.Angiogenesis is important mechanism that aids towards tumor growth, therefore for supplying oxygen and nutrition to support tumor growth.Vascular endothelial growth factor (VEGF) is the major factor that is yielded by the tumor cells. It leads to further amplification of angiogenesis. Inhibition of VEGF could lead to the impediment of the tumor progression (31). Evidence is emerging that LPA signaling contributes to psychiatric disorders. Long-term spatial memory related to LPA pathway was reported by Dash et al. (32). The LPA concentration also states that significant amount of LPA is in the rat brain (33). In the process of the rearrangement of synaptic connections to form neuronal plasticity, neurite retraction and outgrowth is required. This is regulated by LPA signaling pathway (34).LPA1-4 is expressed in ovary and LPA4 expression is observed to be higher in ovary when compared to any other tissue in human. Hormonal stimulation resulted in increasing autotaxin activity in women ovaries (35). LPA/prostaglandin signaling indicates that they have an important role it plays in the embryonic development and maintenance of pregnancy in sheep and pig. The role of LPA signaling in found to be reproduction (36, 37). Research indicates that LPA has significant involvement in male and female reproductive systems.
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