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Expression of plasminogen activator inhibitor‐1 by olfactory ensheathing glia promotes axonal regeneration
Author(s) -
Simón Diana,
MartínBermejo Maria Jesús,
GallegoHernández Maria Teresa,
Pastrana Érika,
GarcíaEscudero Vega,
GarcíaGómez Ana,
Lim Filip,
DíazNido Javier,
Ávila Jesús,
MorenoFlores Maria Teresa
Publication year - 2011
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.21189
Subject(s) - olfactory ensheathing glia , biology , regeneration (biology) , microbiology and biotechnology , axotomy , axon , muller glia , neuroglia , gene silencing , neuroscience , central nervous system , olfactory bulb , stem cell , progenitor cell , biochemistry , gene
Olfactory ensheathing glia (OEG) cells are known to facilitate repair following axotomy of adult neurons, although the molecular mechanisms involved are not fully understood. We previously identified plasminogen activator inhibitor‐1 (PAI‐1), proteinase‐activated receptor‐1 (PAR‐1), and thrombomodulin (TM) as candidates to regulate rat OEG‐dependent axonal regeneration. In this study, we have validated the involvement of these proteins in promoting axonal regeneration by immortalized human OEGs. We studied the effect of silencing these proteins in OEGs on their capacity to promote the regeneration of severed adult retinal ganglion cells (RGCs) axons. Our results support the role of glial PAI‐1 as a downstream effector of PAR‐1 in promoting axon regeneration. In contrast, we found that TM inhibits OEG induced‐axonal regeneration. We also assessed the signaling pathways downstream of PAR‐1 that might modulate PAI‐1 expression, observing that specifically inhibiting Gα i , Rho kinase, or PLC and PKC downregulated the expression of PAI‐1 in OEGs, with a concomitant reduction in OEG‐dependent axon regeneration in adult RGCs. Our findings support an important role for the thrombin system in regulating adult axonal regeneration by OEGs. © 2011 Wiley‐Liss, Inc.