Lysophosphatidylcholine stimulates EGF receptor activation and mesangial cell proliferation: regulatory role of Src and PKC
| Autor: | Mi-Kyung Shin, Vaijinath S. Kamanna, Daeyoung D. Roh, Jung W. Noh, Babu V. Bassa, Shobha H. Ganji |
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| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Indoles MAP Kinase Signaling System Mesangial hypercellularity Biology Maleimides Internal medicine medicine Humans Enzyme Inhibitors Receptor Molecular Biology Protein kinase C Cells Cultured Protein Kinase C Cell Proliferation Flavonoids Kinase MEK inhibitor Receptor transactivation Lysophosphatidylcholines Cell Biology Tyrphostins Cell biology ErbB Receptors Endocrinology src-Family Kinases Mesangial Cells Quinazolines lipids (amino acids peptides and proteins) Signal transduction Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Biochimica et biophysica acta. 1771(11) |
| ISSN: | 0006-3002 |
| Popis: | Lysophosphatidylcholine (LPC), a major component of oxidized-low density lipoproteins (ox-LDL), modulates various pathobiological processes involved in vascular and glomerular diseases. Although several studies have shown increased plasma concentrations of ox-LDL as well as LPC in patients with renal disease, the role of LPC in mesangial cell proliferation and associated signaling mechanisms are not clearly understood. In this study, we have shown that LPC induced the phosphorylation of epidermal growth factor receptor (EGFR), as well as the p42/44 MAP kinases. LPC activated Src-kinase and protein kinase C (PKC), and both Src kinase inhibitor PP-2 and PKC inhibitor inhibited the activation of EGFR by LPC. LPC (5-25 microM) stimulated human mesangial cell proliferation by 4-5 fold. Preincubation of mesangial cells with the Src inhibitor (PP-2), or PKC inhibitor (bisindolylmaleimide GF109203-X), or EGF receptor kinase inhibitor (AG1478), or MEK inhibitor (PD98059) significantly inhibited LPC-mediated mesangial cell proliferation. The data suggest that LPC, by activating Src and PKC signaling pathways, stimulates EGF receptor transactivation and down-stream MAP kinase signaling resulting in mesangial hypercellularity, which is a characteristic feature of diverse renal diseases. |
| Databáze: | OpenAIRE |
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