Progranulin expression is upregulated after spinal contusion in mice.
Progranulin (proepithelin) is a pleiotropic growth-factor associated with inflammation and wound repair in peripheral tissues. It also has been implicated in the response to acute traumatic brain injury as well as to chronic neurodegenerative diseases. To determine whether changes in progranulin expression also accompany acute spinal cord injury, C57BL/6 mice were subjected to mid-thoracic (T9 level) contusion spinal cord injury and analyzed by immunohistochemical and biochemical methods. Whereas spinal cord sections prepared from non-injured laminectomy control animals contained low basal levels of progranulin immunoreactivity in gray matter, sections from injured animals contained intense immunoreactivity throughout the injury epicenter that peaked 7-14 days post injury. Progranulin immunoreactivity colocalized with myeloid cell markers CD11b and CD68, indicating that expression increased primarily in activated microglia and macrophages. Immunoblot analysis confirmed that progranulin protein levels rose after injury. On the basis of quantitative polymerase chain reaction analysis, increased protein levels resulted from a tenfold rise in progranulin transcripts. These data demonstrate that progranulin is dramatically induced in myeloid cells after experimental spinal cord injury and is positioned appropriately both spatially and temporally to influence recovery after injury.
Naphade
Swati B
SB
Department of Molecular and Cellular Biochemistry, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
Kigerl
Kristina A
KA
Jakeman
Lyn B
LB
Kostyk
Sandra K
SK
Popovich
Phillip G
PG
Kuret
Jeff
J
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D005260:Female; D000077155:Granulins; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism; D015213:Neuroimmunomodulation; D000077153:Progranulins; D013116:Spinal Cord / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000378:metabolism*; D013904:Thoracic Vertebrae; D013997:Time Factors; D015854:Up-Regulation; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D039481:CD11b Antigen; D000077155:Granulins; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C120204:Grn protein, mouse