Effect of sulfated GAGs on the expression and activation of MMP‐2 and MMP‐9 in corneal and dermal explant cultures

Abstract

It has been shown previously that hyaluronan (HA) added to fibroblast and keratocyte cell cultures or corneal explant cultures produces an up-regulation of MMP-2 and MMP-9 expression and activation. Here, we examine the effect of sulfated GAG-s, chondroitin 4 and 6 sulfate (CS4, CS6), dermatan sulfate (DS), keratan sulfate (KS) and heparan sulfate (HS) on MMP-2 and 9 expression and activation under the same culture conditions. It appears that CS4 has only minor effects, KS inhibits MMP-2 activation and CS6, DS and HS increase MMP-2 activation in corneal explant cultures. For skin explant cultures, DS, KS and HS strongly increase MMP-9 activation, whereas KS inhibits and DS increases MMP-2 activation. All these effects can be strongly inhibited by the addition of an antibody to CD44, except CS6 and DS. Activation by these two GAGs was only slightly affected, supporting the contention that the effects of HA, CS4, KS and HS are mediated by one of the isoforms of this CD44 receptor. The physio-pathological significance of these results is discussed for cornea and skin ageing, because of the divergent evolution with in vitro ageing of the relative proportions of GAGs synthesised by these two cell types.

Quantitative Analysis of Chondroitin Sulfate in Tear Fluids following Laser in situ Keratomileusis

“…These substances actually fluctuate in the cornea [20,21] and tear fluid [22][23][24] after laser refractive surgery. In addition, Isnard et al [25] reported that CS participates in the activation of matrix metalloproteinases. Based on these facts, CS will interact with transforming growth factor ␤ and the matrix metalloproteinases and participate actively in the corneal woundhealing process.…”

The Effect of Hyaluronic Acid on MMP-9 Expression in Trabecular Meshwork Cell Culture of Patient with Primary Open Angle Glaucoma

“…Penelitian lain oleh Isnard et al (2003), juga menunjukkan peningkatan ekspresi MMP-2 dan MMP-9 pada kultur sel kornea setelah dipapar oleh AH. Selain itu, penelitian oleh Guo et al (2012), juga menunjukkan adanya korelasi antara peningkatan ekspresi MMP-9 dengan pemaparan AH pada kultur sel trabekular meshwork dari pasien glaukoma sudut terbuka primer.…”

“…Kemudian penelitian oleh Fiber et al, 2004, yang menunjukkan bahwa terjadi ekspresi MMP-9 sel Langerhans setelah dipapar dengan AH, meskipun mekanisme yang tepat pada penelitian tersebut belum dipastikan. Selain itu Isnard et al (2003), melakukan penelitian yang menunjukkan bahwa pemberian AH dapat meningkatkan ekspresi MMP-9 kultur sel kornea. Penelitian yang dilakukan oleh Guo et al (2012), juga menunjukkan adanya korelasi antara peningkatan ekspresi MMP-9 dengan paparan AH pada kultur sel trabekular meshwork pasien glaukoma sudut terbuka primer.…”

Bioengineering the Skin–Implant Interface: The Use of Regenerative Therapies in Implanted Devices

“…143 Dermatan sulfate has been shown to participate in cell signaling and reconstruction of the extracellular matrix. 60,107 While is still early to determine the possible use of dermatan sulfate in clinical applications, its interaction with growth factors could be an important factor in therapeutic applications. 161 For both dermatan and hyaluronan, the most probable mechanism of action for their regenerative effect derives from the interaction of the GAG with the cell, regulating receptor signaling without the need of receptor expression.…”