Expression and modulation of matrix metalloproteinase-2 and tissue inhibitors of metalloproteinases in human embryonic CNS stem cells

Paola Frölichsthal-Schoeller, Angelo L. Vescovi, Craig A. Krekoski, Gillian Murphy, Dylan R. Edwards, Peter Forsyth

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The expression and regulation of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) in neuroectodermal precursor cells is undocumented. We report the presence of MMP-2, but no MMP-9, and of all the four known TIMPs in neuroepithelial stem cells isolated from the human CNS. The expression of TIMP-1, TIMP-2 and TIMP-3 was unchanged following stem cells differentiation into neurons and glia. In contrast, while MMP-2 and TIMP-4 were localized to both stem and mature CNS cells, their levels of expression were substantially reduced in the latter. TIMP-4 showed a 23-fold reduction in media conditioned by differentiated cells compared with stem cell-conditioned media, reflecting a 6-fold decrease in mRNA expression. Interestingly, TIMP-4 also differed from the other TIMPs in that it was cell- associated in the stem cells, where this fraction remained unchanged upon differentiation. Hence, regulation of selective MMPs and TIMPs occurs during differentiation of human neural precursors suggesting that MMP-2 and TIMP-4 in particular may perform regulatory roles in the developing CNS.
Original languageEnglish
Pages (from-to)345-351
Number of pages7
JournalNeuroReport
Volume10
Issue number2
Publication statusPublished - 5 Feb 1999

Keywords

  • Human CNS stem cells
  • Matrix metalloproteinases
  • Neural development
  • Neural precursors
  • Tissue inhibitors of metalloproteinases

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