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eISSN: 1643-3750

Acetylsalicylic acid-dependent inhibition of collagen biosynthesis and ß1 -integrin signaling in cultured fibroblasts

Arkadiusz Surażyński, Jerzy Pałka, Sławomir Wołczyński

Med Sci Monit 2004; 10(6): BR175-179

ID: 11675

Published: 2004-06-03


Background:Non-steroid anti-inflammatory drugs (NSAIDs) are known inhibitors of collagen biosynthesis in animal tissues and cell cultures. The mechanism of their action on collagen biosynthesis involves inactivation of prolidase, the enzyme that recovers proline from collagen degradation products for collagen re-synthesis. In fibroblasts, prolidase activity is stimulated through a signal induced by an activated β[sub]1[/sub] -integrin receptor that contributes to an increase in enzyme phosphorylation. To discover whether this is an underlying mechanism of acetylsalicylic acid-dependent inhibition of collagen biosynthesis in fibroblasts was the aim of this study.
Material/Methods: Control and acetylsalicylic acid-treated confluent human skin fibroblasts were compared with respect to collagen biosynthesis ([[sup]3[/sup]H]proline incorporation assay), prolidase activity (colorimetric assay) and the expressions of prolidase and some signaling proteins (Western immunoblot analysis).Results: In cells treated with acetylsalicylic acid, a concomitant decrease in prolidase activity, prolidase phosphorylation (at the threonine residue), and collagen biosynthesis were observed. This was accompanied by a decrease in the expressions of SOS and phosphorylated MAP kinases, ERK1 and ERK2, but not FAK or Grab2. This suggests that a decrease in prolidase activity may contribute to a decrease in the biosynthesis of proline-containing proteins, such as collagen and SOS. A decrease in collagen biosynthesis decreases the interaction of the protein with the β[sub]1[/sub]-integrin receptor (extracellular process), disturbing signaling (intracellular process).Conclusions: The inhibitory effect of acetylsalicylic acid on collagen biosynthesis in fibroblasts is coupled to the inhibition of prolidase phosphorylation (but not expression) and down-regulation of the intracellular signal transmitted by the β[sub]1[/sub] -integrin receptor.

Keywords: Antigens, CD29 - metabolism, Aspirin - pharmacology, Cells, Cultured, Collagen - biosynthesis, Collagen - metabolism, Dipeptidases - metabolism, Fibroblasts, Humans, Phosphothreonine - metabolism, Signal Transduction - drug effects, Skin - drug effects, Skin - metabolism, Antigens, CD29 - metabolism, Aspirin - pharmacology, Cells, Cultured, Collagen - metabolism, Dipeptidases - metabolism, Fibroblasts, Humans, Phosphothreonine - metabolism, Signal Transduction - drug effects, Skin - metabolism



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