Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) expression is regulated by multiple neural differentiation signals
Article first published online: 18 MAY 2006
Journal of Neurochemistry
Volume 98, Issue 1, pages 234–247, July 2006
How to Cite
Jaworski, D. M. and Pérez-Martínez, L. (2006), Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) expression is regulated by multiple neural differentiation signals. Journal of Neurochemistry, 98: 234–247. doi: 10.1111/j.1471-4159.2006.03855.x
- Issue published online: 30 MAY 2006
- Article first published online: 18 MAY 2006
- Received November 11, 2005; revised manuscript received February 14, 2006; accepted February 15, 2006.
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 α3 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.