Galectin-3 mediates post-ischemic tissue remodeling.
Galectin-3 (Gal-3) is a member of a class of carbohydrate-binding proteins and plays a role in a number of cellular functions such as cell proliferation, angiogenesis and differentiation. We observed an up-regulated expression of Gal-3 in the ischemic brain following transient middle cerebral artery occlusion in rats. Compared to the brain of sham-operated rats, the expression of Gal-3 was increased in the ischemic striatum at day 1 of reperfusion. The number of Gal-3+ cells in the ischemic brain was further increased at day 2 and day 3, and peaked at day 7 of reperfusion. The up-regulated expression of Gal-3 persisted from day 14 to 2 months after reperfusion. Double staining showed co-localization of Gal-3 with OX-42+ cells, glial fibrillary acidic protein (GFAP)+ and ED1+ cells, suggesting that activated microglia/infiltrating macrophages and activated astrocytes are the primary source of Gal-3 in the ischemic brain. In the in vitro setting, Gal-3 treatment dose-dependently stimulated the proliferation of endothelial cells and neural progenitors. Blockade of Gal-3 activity by infusing a neutralizing antibody against Gal-3 into the ischemic striatum decreased ischemia-induced angiogenesis and the proliferation of neural progenitors. These results suggest that Gal-3 expressed by activated microglia/infiltrating macrophages and astrocytes in the ischemic brain may play a role in post-ischemic tissue remodeling by enhancing angiogenesis and neurogenesis.
Yan
Yi-Ping
YP
Department of Neurological Surgery, University of Wisconsin-Madison, 600 Highland Ave. Madison, WI 53792, USA.
Lang
Bradley T
BT
Vemuganti
Raghu
R
Dempsey
Robert J
RJ
D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000098:blood supply / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D037502:Galectin 3 / Q000378:metabolism*; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D015424:Reperfusion; D015854:Up-Regulation
D037502:Galectin 3