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Tissue Inhibitor of Metalloproteinase‐2 (TIMP‐2) expression is regulated by multiple neural differentiation signals
Author(s) -
Jaworski Diane M.,
PérezMartínez Leonor
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03855.x
Subject(s) - microbiology and biotechnology , progenitor cell , cellular differentiation , biology , neurogenesis , extracellular matrix , retinoic acid , integrin , cell culture , stem cell , cell , biochemistry , genetics , gene
Neuronal differentiation requires exquisitely timed cell cycle arrest for progenitors to acquire an appropriate neuronal cell fate and is achieved by communication between soluble signals, such as growth factors and extracellular matrix molecules. Here we report that the expression of TIMP‐2, a matrix metalloproteinase inhibitor, is up‐regulated by signals that control proliferation (bFGF and EGF) and differentiation (retinoic acid and NGF) in neural progenitor and neuroblastoma cell lines. TIMP‐2 expression coincides with the appearance of neurofilament‐positive neurons, indicating that TIMP‐2 may play a role in neurogenesis. The up‐regulation of TIMP‐2 expression by proliferate signals suggests a role in the transition from proliferation to neuronal differentiation. Live labeling experiments demonstrate TIMP‐2 expression only on α 3 integrin‐positive cells. Thus, TIMP‐2 function may be mediated via interaction with integrin receptor(s). We propose that TIMP‐2 represents a component of the neurogenic signaling cascade induced by mitogenic stimuli that may withdraw progenitor cells from the cell cycle permitting their terminal neuronal differentiation.