Phosphoenolpyruvate-dependent inhibition of collagen biosynthesis, ¦Á₂¦Â₁ integrin and IGF-I receptor signaling in cultured fibroblasts

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• 作者：Ewa Karna and Jerzy A. Palka
• 关键词：α ; 2β ; 1 Integrin receptor ; Collagen biosynthesis ; Fibroblasts ; IGF ; I receptor ; Phosphoenolpyruvate ; Prolidase
• 刊名：Molecular and Cellular Biochemistry
• 出版年：2008
• 出版时间：August, 2008
• 年：2008
• 卷：315
• 期：1-2
• 页码：61-67
• 全文大小：368.8 KB

文摘

The mechanism of collagen biosynthesis regulation is not fully understood. The finding that prolidase plays an important role in collagen biosynthesis and phosphoenolpyruvate inhibits prolidase activity “in vitro” led to evaluate its effect on collagen biosynthesis in cultured human skin fibroblasts. Confluent fibroblasts were treated with millimolar concentrations (1–4 mM) of phosphoenolpyruvate monopotassium salt (PEP) for 24 h. It was found that PEP-dependent decrease in prolidase activity and expression was accompanied by parallel decrease in collagen biosynthesis. However, the experiments with inhibitor of PEP production, 3-mercaptopicolinate revealed no direct correlation between collagen biosynthesis and prolidase activity and expression. Since insulin-like growth factor (IGF-I) is the most potent stimulator of both collagen biosynthesis and prolidase activity, and prolidase is regulated by β₁ integrin signaling, the effect of PEP on IGF-I receptor (IGF-IR) and β₁ integrin receptor expressions were evaluated. It was found that the exposure of the cells to 4 mM PEP contributed to a decrease in IGF-IR and β₁ integrin receptor expressions. The data suggest that PEP-dependent decrease of collagen biosynthesis in cultured human skin fibroblasts may undergo through depression of α₂β₁ integrin and IGF-IR signaling. The hypothetical mechanism of the role of prolidase in IGF-IR, β₁ integrin receptor expressions, and clinical significance of the process are discussed.