Matrix metalloproteinase expression in the olfactory epithelium

Abstract

The olfactory epithelium contains neuronal progenitor cells capable of continuous neurogenesis and is a unique model for studying neural degeneration, regeneration, axon outgrowth and recovery from injury. Matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs), have been implicated in cell turnover, development, migration, and metastatic processes. We used Western blot and immunohistochemistry to determine whether MMP-2 and associated proteins TIMP-2 and membrane type 1 matrix metalloproteinase (MT1-MMP) are present in the olfactory epithelium of mice. We found MMP-2 expression localized to the olfactory basal cells and immature neurons. After injury-induced neural degeneration, MMP-2 and MT1-MMP levels decreased while TIMP-2 levels increased. However, following 35 days of neurogenesis and cell replacement TIMP-2 and MT1-MMP returned to control levels. The results show a correlation between MMP and TIMP levels and the stages of neural degeneration, regeneration and recovery of the olfactory epithelium following injury.

Olfactory Horizontal Basal Cells Demonstrate a Conserved Multipotent Progenitor Phenotype

“…Similarly, in the OE, local ensheathing cells (which secrete basal lamina ECM), are ideally situated to detect the loss of mature ORN axons and remodel basal lamina via MMPs or ECM secretion in a highly localized manner (summarized in Fig. 9) (Au and Roskams, 2003;Tsukatani et al, 2003).…”

Response of matrix metalloproteinase-9 to olfactory nerve injury

“…MMP-9 is often elevated immediately after injury, particularly during the onset of inflammation, although its role is not yet clear [4,9,10]. MMP-2 is often constitutively expressed [11] or expressed after the initial response to injury [12]. Recent studies of injury in the CNS have implicated rapid MMP-9 upregulation in early stages following acute CNS injury, including traumatic brain injury [10], ischemia [5,6,8,13] and spinal cord injury [9].…”

Matrix Rigidity Activates Wnt Signaling through Down-regulation of Dickkopf-1 Protein

“…Although the specific microenvironment of tissue-invasive cell types varies, a common feature often includes a three-dimensional collagen scaffold penetrated by invasive cells. Recent studies suggest that common mechanisms can be adopted by diverse cell types to invade three-dimensional collagen gels (11)(12)(13)(14)(15).…”