title: Transient expression of endothelins in the amoeboid microglial cells in the developing rat brain.
abstract: Amoeboid microglial cells (AMC) which transiently exist in the corpus callosum in the postnatal rat brain expressed endothelins (ETs), specifically endothelin-1 (ET-1) and ET3 as revealed by real time RT-PCR. ET immunoreactive AMC occurred in large numbers at birth, but were progressively reduced with age and were undetected in 14 days. In rats subjected to hypoxia exposure, ET immunoexpression in AMC was reduced but the incidence of apoptotic cells was not increased when compared with the control suggesting that this was due to its downregulation that may help regulate the constriction of blood vessels bearing ET-A receptor. AMC were endowed ET-B receptor indicating that ET released by the cells may also act via an autocrine manner. In microglia activated by lipopolysaccharide (LPS), ET-1 mNA expression coupled with that of monocyte chemoattractant protein (MCP-1) and stromal derived factor-1 (SDF-1) was markedly increased; ET-3 mRNA, however, remained unaffected. AMC exposed to oxygen glucose deprivation (OGD) in vitro resulted in increase in both ET-1 and ET-3 mRNA expression. It is suggested that the downregulated ETs expression in vivo of AMC subjected to hypoxia as opposed to its upregulated expression in vitro may be due to the complexity of the brain tissue. Furthermore, the differential ET-1 and ET-3 mRNA expression in LPS and OGD treatments may be due to different signaling pathways independently regulating the two isoforms. The present novel finding has added microglia as a new cellular source of ET that may take part in multiple functions including regulating vascular constriction and chemokines release.
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Chun-Yun
authors.initials: CY
authors.lastname: Wu
authors.forename: Charanjit
authors.initials: C
authors.lastname: Kaur
authors.forename: Jia
authors.initials: J
authors.lastname: Lu
authors.forename: Qiong
authors.initials: Q
authors.lastname: Cao
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Guo
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Sivakumar
authors.forename: Eng-Ang
authors.initials: EA
authors.lastname: Ling
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000196:embryology* / Q000254:growth & development* / Q000648:ultrastructure; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D019334:Endothelin-3 / Q000235:genetics / Q000378:metabolism; D016232:Endothelins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D020925:Hypoxia-Ischemia, Brain / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008833:Microcirculation / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D017628:Microglia / Q000378:metabolism* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000378:metabolism; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D019332:Endothelin-1; D019334:Endothelin-3; D016232:Endothelins; D012333:RNA, Messenger; D017466:Receptors, Endothelin