Upregulation of pleiotrophin gene expression in developing microvasculature, macrophages, and astrocytes after acute ischemic brain injury.
Pleiotrophin (PTN) is a heparin-binding, 18 kDa secretory protein that functions to induce mitogenesis, angiogenesis, differentiation, and transformation in vitro. PTN gene (Ptn) expression is highly regulated during development and is highest at sites in which mitogenesis, angiogenesis, and differentiation are active. In striking contrast, with the exception of the neuron, the Ptn gene is only minimally expressed in adults. We now demonstrate that Ptn gene expression is strikingly upregulated within 3 d in OX42-positive macrophages, astrocytes, and endothelial cells in areas of developing neovasculature after focal cerebral ischemia in adult rat. Ptn gene expression remains upregulated in these same cells and sites 7 and 14 d after ischemic injury. However, expression of the Ptn gene is significantly decreased in cortical neurons 6 and 24 hr after injury and is undetectable in degenerating neurons at day 3. Neurons in contralateral cortex continue to express Ptn in levels equal to control, uninjured brain. It is suggested that PTN may have a vital role in neovascular formation in postischemic brain and that postischemic brain is an important model in which to analyze sequential gene expression in developing neovasculature. In contrast, Ptn gene expression in injured neurons destined not to recover is strikingly reduced, and potentially its absence may contribute to the failure of the neuron to survive.
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Department of Medicine, Division of Growth Regulation, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
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D000208:Acute Disease; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001921:Brain / Q000098:blood supply / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics*; D016207:Cytokines / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008833:Microcirculation / Q000502:physiology; D008934:Mitogens / Q000235:genetics*; D018919:Neovascularization, Physiologic / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains
D002352:Carrier Proteins; D016207:Cytokines; D008934:Mitogens; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C066845:pleiotrophin