Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extracellular lysophosphatidate (LPA) signalling is regulated by the balance of LPA formation by autotaxin (ATX) versus LPA degradation by lipid phosphate phosphatases (LPP) and by the relative expressions of six G-protein-coupled LPA receptors. These receptors increase cell proliferation, migration, survival and angiogenesis. Acute inflammation produced by tissue damage stimulates ATX production and LPA signalling as a component of wound healing. If inflammation does not resolve, LPA signalling becomes maladaptive in conditions including arthritis, neurologic pain, obesity and cancers. Furthermore, LPA signalling through LPA1 receptors promotes fibrosis in skin, liver, kidneys and lungs. LPA also promotes the spread of tumours to other organs (metastasis) and the pro-survival properties of LPA explain why LPA counteracts the effects of chemotherapeutic agents and radiotherapy. ATX is secreted in response to radiation-induced DNA damage during cancer treatments and this together with increased LPA1 receptor expression leads to radiation-induced fibrosis. The anti-inflammatory agent, dexamethasone, decreases levels of inflammatory cytokines/chemokines. This is linked to a coordinated decrease in the production of ATX and LPA1/2 receptors and increased LPA degradation through LPP1. These effects explain why dexamethasone attenuates radiation-induced fibrosis. Increased LPA signalling is also associated with cardiovascular disease including atherosclerosis and deranged LPA signalling is associated with pregnancy complications including preeclampsia and intrahepatic cholestasis of pregnancy. LPA contributes to chronic inflammation because it stimulates the secretion of inflammatory cytokines/chemokines, which increase further ATX production and LPA signalling. Attenuating maladaptive LPA signalling provides a novel means of treating inflammatory diseases that underlie so many important medical conditions.
 ...
PMID:Signalling by lysophosphatidate and its health implications. 3245 53


<< Previous 1 2 3 4