Faber-Elman Anat. Lavie Vered. Schvartz Iris. Shaltiel Shmuel. Schwartz
Michal [a].
Vitronectin overrides a negative effect of TNF-alpha on astrocyte migration, FASEB Journal 9(15) :1605-1613, 1995.
Abstract
Morphogenesis and tissue repair require appropriate cross-talk between the
cells and their surrounding milieu, which includes extracellular components
and soluble factors, e.g., cytokines and growth factors. The present work
deals with this communication needed for recovery after axotomy in the
central nervous system (CNS). The failure of CNS axons to regenerate after
axonal injury has been attributed, in part, to astrocyte
failure to repopulate the injury site. The goal of this work was to provide
an in vitro model to mimic the in vivo response of
astrocytes to nerve injury and to find ways to modulate this
response and create a milieu that favors astrocyte
migration and repopulation of the injury site. In an
astrocyte scratch wound model, we blocked
astrocyte migration by tumor necrosis
factor alpha (TNF-alpha). This effect could not he reversed by
astrocyte migration-inducing factors such
as transforming growth factor beta-1 (TGF-beta-1) or by any of the tested
extracellular matrix (ECM) components (laminin and fibronectin) except for
vitronectin (Vn). Vn, added together with TNF-alpha, counteracted the
TNF-alpha blockage and allowed a massive migration of
astrocytes (not due to cell proliferation) beyond that
allowed by Vn only. Heparan sulfate proteoglycans (HSPG) were shown to be
involved in the migration. The results may be relevant to
regeneration of CNS axons, and may also provide an example that an
extracellular component (Vn) can overcome and neutralize a negative effect of
a growth factor/cytokine (TNF-alpha) and can act in synergy with other
features of this cytokine to promote a necessary function (e.g., cell
migration) that is otherwise inhibited.
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