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Review
. 2009 Apr;88(4):676-82.
doi: 10.1016/j.exer.2008.11.023. Epub 2008 Dec 6.

Extracellular matrix turnover and outflow resistance

Kate E Keller  1 , Mini Aga, John M Bradley, Mary J Kelley, Ted S Acott
Affiliations
Review

Extracellular matrix turnover and outflow resistance

Kate E Keller et al. Exp Eye Res. 2009 Apr.

Abstract

Normal homeostatic adjustment of elevated intraocular pressure (IOP) involves remodeling the extracellular matrix (ECM) of the trabecular meshwork (TM). This entails sensing elevated IOP, releasing numerous activated proteinases to degrade existing ECM and concurrent biosynthesis of replacement ECM components. To increase or decrease IOP, the quantity, physical properties and/or organization of new components should be somewhat different from those replaced in order to modify outflow resistance. ECM degradation and replacement biosynthesis in the outflow pathway must be tightly controlled and focused to retain the complex structural organization of the tissue. Recently identified podosome- or invadopodia-like structures (PILS) may aid in the focal degradation of ECM and organization of replacement components.

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Figures

Figure 1
Figure 1
Schematic showing the multi-domain structure of MMPs, ADAMs and ADAMTSs. Zinc is histidine-ligated into the catalytic site and cleavage of the prodomain disrupts the thiol-zinc bond and activates the enzyme, a mechanism known as the cysteine-switch. The hemopexin domains of MMPs function in substrate recognition, targeting or localization and can homodimerize to augment proteolytic activity. ADAMs can interact with various integrins via the disintegrin domain and with a number of intracellular binding motifs through its cytosolic tail. ADAMTSs can interact with sulfated GAGs and fibronectin and can be proteolytically cleaved in the spacer region. The number of C-terminal thrombospondin domains varies from 0–14 between family members.
Figure 2
Figure 2
Podosome-like structures formed by porcine TM cells in culture. (A) Immuno-colocalization of MMP2 (green) and MMP14 (red) to PILS. Blue = F-actin phalloidin staining. (B) Colocalization of a typical PILS component, cortactin (green), and MMP2 (red) to a podosome rosette structure. Bar = 10 µm. (C) Colocalization of cortactin (green) and a neo-epitope of versican that is created by ADAMTS4 proteolysis (red). (D) Lower magnification image showing colocalization of cortactin (green) and the ADAMTS4-generated neo-epitope of versican (red) to PILS. Blue = F-actin phalloidin staining.
Figure 3
Figure 3
Role of TIMP2 in the activation of pro-MMP2. The N-terminus of TIMP2 binds to one molecule of MMP14 at the cell surface. Concomitantly, the C-terminus of TIMP2 binds to the C-terminus of pro-MMP2. This trimeric complex then recruits another molecule of MMP14, which cleaves the propeptide to activate MMP2. This schematic depicts the simplest mechanism of pro-MMP2 activation, but other molecules are likely to be involved, e.g. CD44, integrins, etc.
See this image and copyright information in PMC

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References

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