Protease nexin I expression is up-regulated in human skeletal muscle by injury-related factors
✍ Scribed by Corinne Mbebi; Daniel Hantaï; Martine Jandrot-Perrus; Marie-Agnès Doyennette; Martine Verdière-Sahuqué
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 385 KB
- Volume
- 179
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Protease nexin I is a 43-50 kDa glycoprotein capable of inhibiting a number of serine proteases. In cultured differentiated human skeletal muscle (myotubes), we previously found that protease nexin I was localized in patches at their surface where it was active and able to inhibit thrombin. To understand the role of skeletal muscle protease nexin I after injury or in inflammatory conditions where thrombin might be extravasated by blood vessels, we examined the role of inflammatory factors on protease nexin I synthesis and secretion by myotubes in culture. By enzyme-linked immunosorbent assay (ELISA) and Western blotting, we found that this serine protease inhibitor is secreted by cultured human myotubes. Protease nexin I secretion is stimulated by tumor necrosis factor-␣, transforming growth factor- and interleukin-1. Complex formation experiments with labeled thrombin reveal active protease nexin I bound to the surface of the treated cells. Secreted protease nexin I-thrombin complex was enhanced in the presence of transforming growth factor- and tumor necrosis factor-␣. Protease nexin I mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analysis. Whatever the conditions, no significantly different levels were observed, indicating that the changes in cell and media protease nexin I concentration are elicited at the translational/posttranslational levels. Immunocytochemical studies on human skeletal muscle biopsies of patients suffering from inflammatory myopathies showed an overexpression of protease nexin I together with the above inflammatory factors. These findings suggest that skeletal muscle protease nexin I might play a role after injury or inflammatory pathologies.