title: Erythropoietin promotes axonal regeneration after optic nerve crush in vivo by inhibition of RhoA/ROCK signaling pathway.
abstract: We investigated whether the RhoA/ROCK pathway was involved in the effect of erythropoietin (EPO) to promote retinal ganglion cells (RGCs) axonal regeneration in a rat optic nerve crush (ONC) model. We demonstrated that both EPO and ROCK inhibitor Y-27632 significantly enhanced RGCs survival and axon regeneration in vivo, and the effects of these agents were additive. Expression of active-RhoA was decreased after EPO or Y-27632 per pull down assay and affinity precipitation. Administration of EPO and Y-27632 cocktail resulted in even more RhoA inactivation, decreased expression of ROCK-1 and ROCK-2, and increased expression of growth associated protein-43 (GAP-43) protein per immunohistochemistry and western blot analysis. Down-regulation of active-RhoA, ROCK-1, and ROCK-2 expression by EPO coincided with the appearance of larger numbers of regenerating axons. In conclusion, the RhoA/ROCK signaling pathway was involved in the EPO effect to promote RGCs axon regeneration after ONC.
authors: Department of Ophthalmology, Ruijin Hospital Affiliated Medical School, Shanghai Jiaotong University, 197 Ruijin No. 2 Road, 200025 Shanghai, China.
authors: Haibo
authors: H
authors: Tan
authors: Yisheng
authors: Y
authors: Zhong
authors: Xi
authors: X
authors: Shen
authors: Yu
authors: Y
authors: Cheng
authors: Qin
authors: Q
authors: Jiao
authors: Lianfu
authors: L
authors: Deng
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000187:drug effects*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004921:Erythropoietin / Q000494:pharmacology*; D019922:GAP-43 Protein / Q000096:biosynthesis / Q000235:genetics; D007150:Immunohistochemistry; D008297:Male; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000187:drug effects*; D009900:Optic Nerve / Q000166:cytology* / Q000254:growth & development*; D020221:Optic Nerve Injuries / Q000473:pathology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013477:Superior Colliculi / Q000166:cytology / Q000187:drug effects; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000502:physiology*
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D019922:GAP-43 Protein; D011725:Pyridines; D004921:Erythropoietin; C108830:Y 27632; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein