systolic and/or systemic hypertension which is worsened by high dietary intake of salt. These effects are thought to be due to the loss of EP2's vasodilation effects and/or ability to increase the urinary excretion of salt. Bone EP2-deficient mice exhibit impaired generation of osteoclasts (cells that break down bone tissue) due to a loss in the capacity of osteoblastic cells to stimulate osteoclast formation. These mice have weakened bones compared with the wild type animals. When administered locally or systemically to animals, EP2-selective agonists stimulate the local or systemic formation of bone, augment bone mass, and accelerate the healing of fractures and other bone defects in animal models. Nervous system EP2 deficient mice exhibit reduced Oxidative stress and beta amyloid formation. Activation of this receptor also has neuroprotective effects in models of Alzheimer's disease, Amyotrophic lateral sclerosis, multiple sclerosis, and stroke while its inhibition reduces Epileptic seizure. EP2 signaling can also increase stroke injury via neurons in a mice model according to a PNAS paper. EP2 receptors on either nerve or Neuroglia cells of the peripheral and central nervous system act to promote pain perception, which are caused by inflammation, muscle stretch, temperature, and physical stimuli (see allodynia) in mice. A 2021 study found that inhibition of myeloid cell EP2 signalling can reverse or prevent an inflammation element of brain-ageing in mice. Malignancy The EP2 receptor can act as a tumor promoter. EP2 gene knockout mice have less lung, breast, skin, and colon cancers following exposure to carcinogens. Knockout of this gene in mice with the adenomatous polyposis coli mutation also causes a decrease in the size and number of pre-cancerous intestinal polyps that the animals develop. These effects are commonly ascribed to the loss of EP2-mediated: Vascular endothelial growth factor production and thereby of tumor vascularization; regulation of endothelial cell motility and survival; interference with transforming growth factor-β's anti-cell proliferation activity; and, more recently, regulation of host anti-tumor immune responses. Clinical significance Therapeutics Preclinical studies, as outlined above, indicate that EP2 may be a target for treating and/or preventing particular human disorders involving: allergic diseases such as asthma and rhinitis, particularly aspirin-exacerbated respiratory disease (AERD); glaucoma; various diseases of the nervous system; fractures, osteoporosis, and other bone abnormalities; pulmonary fibrosis; certain forms of malignant disease such as colon cancer including those that arise from Adenomatous polyposis coli mutations; and salt-sensitive forms of hypertension; This receptor has also been suggested