Airway Epithelial Cell Migration Dynamics: MMP-9 Role in Cell–Extracellular Matrix Remodeling

Abstract

Cell spreading and migration associated with the expression of the 92-kD gelatinase (matrix metalloproteinase 9 or MMP-9) are important mechanisms involved in the repair of the respiratory epithelium. We investigated the location of MMP-9 and its potential role in migrating human bronchial epithelial cells (HBEC). In vivo and in vitro, MMP-9 accumulated in migrating HBEC located at the leading edge of a wound and MMP-9 expression paralleled cell migration speed. MMP-9 accumulated through an actin-dependent pathway in the advancing lamellipodia of migrating cells and was subsequently found active in the extracellular matrix (ECM). Lamellipodia became anchored through primordial contacts established with type IV collagen. MMP-9 became amassed behind collagen IV where there were fewer cell–ECM contacts. Both collagen IV and MMP-9 were involved in cell migration because when cell–collagen IV interaction was blocked, cells spread slightly but did not migrate; and when MMP-9 activation was prevented, cells remained fixed on primordial contacts and did not advance at all. These observations suggest that MMP-9 controls the migration of repairing HBEC by remodeling the provisional ECM implicated in primordial contacts.

Native matrix-based human lung alveolar tissue model in vitro: studies of the reparatory actions of mesenchymal stem cells

“…MMP-9, and their up-regulation reflects similar tendencies reported by other authors (Braber et al 2011;Overbeek et al 2013). In general, expression of MMPs in lung tissue is described as a characteristic of tissue remodeling associated with various biological processes, such as development, inflammation, migration of cells, wound repair and other (Legrand et al 1999;Itoh et al 2002;Barnes et al 2003;Wolf et al 2003;Greenlee et al 2007;Crosby and Waters 2010). Secretion of pro-inflammatory chemokine GROa was increased by CSE in our native matrix model in contrast to some other reports (Victoni et al 2014) suggesting that study model and matrix origin might be important.…”

Matrilysin (Matrix Metalloproteinase-7) Mediates E-Cadherin Ectodomain Shedding in Injured Lung Epithelium

“…Although other MMPs, such as gelatinase B (MMP-9), may function in lung repair by cleaving extracellular matrix proteins, 31,42 our data suggest that matrilysin facilitates migration of surviving cells by promoting reorganization of cell-cell junctions. Matrilysin can degrade many extracellular matrix proteins in vitro, including fibronectin, 43 a prominent component of the provisional matrix in injured lungs.…”

Gelatinase-mediated migration and invasion of cancer cells

“…For example, human bronchial epithelial cells secrete MMP-9 in an actin-dependent manner to the leading edge of migrating cells. MMP-9 activity in these cells was required specifically for cell migration and not adhesion or spreading (Legrand et al, 1999). Although the mechanisms by which the MMP-9 is localized on the cell surface appear to be redundant, there are a few important similarities.…”

“…The gelatinases participate also in wound repair (Legrand et al, 1999;Mohan et al, 2002;Salonurmi et al, 2004) and are typically expressed from the beginning to the end of the healing process (Salo et al, 1994). Gelatinases and other MMPs are also able to participate in the regulation of apoptosis.…”