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Phosphoenolpyruvate-dependent inhibition of collagen biosynthesis, α2β1 integrin and IGF-I receptor signaling in cultured fibroblasts

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Abstract

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.

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  1. Department of Medicinal Chemistry, Medical University in Bialystok, Kilińskiego 1, 15-089, Bialystok, Poland

    Ewa Karna & Jerzy A. Palka

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  1. Ewa Karna
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  2. Jerzy A. Palka
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Correspondence to Jerzy A. Palka.

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Karna, E., Palka, J.A. Phosphoenolpyruvate-dependent inhibition of collagen biosynthesis, α2β1 integrin and IGF-I receptor signaling in cultured fibroblasts. Mol Cell Biochem 315, 61–67 (2008). https://doi.org/10.1007/s11010-008-9789-2

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  • DOI: https://doi.org/10.1007/s11010-008-9789-2

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