Thy-1-Mediated phosphatidylinositol turnover in cultured rat glomerular mesangial cell

✍ Scribed by Mako Narisawa-Saito; Satoshi Kimura; Naoshi Fujiwara; Takashi Oite; Koki Shimoji; Fujio Shimizu

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 592 KB
• Volume: 168
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/(sici)1097-4652(199609)168:3<705::aid-jcp23>3.0.co;2-w

✦ Synopsis

Thy-1 glycoprotein is expressed in rat glomerular mesangial cells, and anti-Thy-1 nephritis induced by anti-Thy-1 antibodies is a model of human renal diseases. In this study, we examined Thy-1 -mediated biological reactions in cultured rat glomerular mesangial cells utilizing two anti-Thy-1 monoclonal antibodies (mAbs), 1-22-3 and OX-7. Incubation of the cells with these mAbs resulted in increased inositol trisphosphate UP,) levels. The rise in IP3 produced by mAb 1 -22-3 was greater than that produced by mAb OX-7 at the same dose. Incubation of mesangial cells with these mAbs resulted in an increase in the intracellular free calcium concentration ([Ca*+Ii). mAb 1-22-3 induced a sustained increase in [Ca'+]i, while that induced by mAb OX-7 lasted 1-2 min, then decreased to the basal level. An transient increase in [Ca"]i was also observed in Caz+-free medium, indicating that these [Ca'+]i increases are due to release of Ca" from internal stores by IP3 without calcium flux across cell membrane. When cells were pretreated with protein tyrosine kinase (PTK) inhibitors (herbimycin A or genistein), Thy-1 -mediated increases in [Ca"]i were inhibited. These data suggest that Thy-1 induces the production of IP3 (including inositol 1,4,5-triphosphate, an intracellular Ca2+-releasing factor) and that PTKs may contribute to the Thy-1 mediated elevation of [Ca"]i which presumably results from phospholipase C activation following Thy-1 -mediated signaling in rat mesangial cells.