Effect of Hyaluronan on MMP Expression and Activation

Abstract

Matrix metalloproteases (MMPs) play a crucial role in tissue remodelling in a variety of physiological and pathological processes. Hyaluronan is also involved in the same processes. Several cytokines and growth factors are involved in the regulation of the biosynthesis of hyaluronan and also of MMPs. The activity of MMPs has been shown to be regulated at the level of transcription and activation of the zymogen form. In order to explore the possible relationship between matrix components and especially hyaluronan, we studied the effect of hyaluronan on MMP expression (biosynthesis and activation) in the culture of human skin fibroblasts and corneal keratocytes (explant cultures and cell cultures). These cells were shown to exhibit distinct phenotypes as far as matrix biosynthesis is concerned. Using a synthetic substrate N-Suc(ala)3pNA, we measured elastase-type endopeptidase activity produced by fibroblasts and keratocytes and characterized the MMPs by zymography. Hyaluronan added to fibroblast cultures stimulated the membrane-bound elastase-type endopeptidase activity in a dose dependent fashion. Similar results were obtained with keratocyte cultures. In the presence of 1 mg/ml hyaluronan there was an increase in MMP expression and also an activation of latent MMPs both by fibroblasts and keratocytes.

Low Molecular Weight Hyaluronan Activates Cytosolic Phospholipase A2α and Eicosanoid Production in Monocytes and Macrophages

“…Supernatants were harvested and stored at Ϫ80°C. PGE 2 , PGD 2 , 15(S)-HETE, LTB 4 , and LTC 4 (Cayman Chemicals) or LXA 4 (Oxford Biomedical Research, Rochester Hills, MI,) determination was performed with commercially available EIA kits. Detection limits of the EIA kits were as follows: 15 pg/ml for PGE 2 , 55 pg/ml for PGD 2 , 170 pg/ml for 15(S)-HETE, 13 pg/ml for LTB 4 , 10 pg/ml for LTC 4 , and 20 pg/ml for LXA 4 .…”

Roles of Pseudomonas aeruginosa Autoinducers and their Degradation Products, Tetramic acids, in Bacterial Survival and Behavior in Ecological Niches

“…Elastase-type endopeptidase activity was determined using NSuc(ala)3pNA (Sigma, St Louis, MO), as described previously (14). For the pyocyanin assay, 5 ml of bacterial supernatant was extracted with 3 ml of chloroform, and then re-extracted into 1 ml of 0.2 N HCl.…”

The effects of 4-methylumbelliferone on hyaluronan synthesis, MMP2 activity, proliferation, and motility of human aortic smooth muscle cells

“…Moreover, ECM components can modify MMP expression and activation, as recently outlined by Iida and collaborators (Iida et al 2007). In this context, HA was shown to induce MMP activity in fibroblasts (Isnard et al 2001), lung carcinoma cells (Zhang et al 2002), and chondrocytes (Takahashi et al 1999;Ohno et al 2006).…”