Butyrate-induced collagen biosynthesis in cultured fibroblasts is independent on alpha2beta1 integrin signalling and undergoes through IGF-I receptor cascade.
The potential role of butyrate to modulate cellular metabolism through integrin receptor led to evaluation of its effect on collagen biosynthesis in cultured fibroblasts. Confluent human dermal fibroblasts were treated with 2 mM and 4 mM of sodium butyrate (NaB) for 48 h. It was found that butyrate induced collagen biosynthesis and prolidase activity independently of alpha2beta1 integrin signaling. The expressions of both alpha2 and beta1 integrin subunits as well as integrin-induced activation of focal adhesion kinase (FAK) were not affected in the cells treated with NaB. Since insulin-like growth factor-I (IGF-I) is the most potent stimulator of collagen biosynthesis in fibroblasts, the effect of butyrate on IGF-I receptor (IGF-IR) expression was evaluated. It was found that the exposure of the cells to 4 mM butyrate contributed to a distinct increase in IGF-IR. It was accompanied by a parallel increase in the expression of Sos protein and MAP-kinases (ERK1, ERK2). The data suggests that butyrate-dependent stimulation of collagen biosynthesis in cultured human skin fibroblasts undergoes through IGF-IR signaling.
Department of Medicinal Chemistry, Medical University in Białystok, Kilińskiego 1, 15-089 Białystok, Poland.
Ewa
E
Karna
Wojciech
W
Miltyk
Jerzy A
JA
Pałka
D015153:Blotting, Western; D002087:Butyrates / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis*; D004150:Dipeptidases / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D038982:Integrin alpha2beta1 / Q000502:physiology*; D011392:Proline / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020664:Son of Sevenless Proteins / Q000378:metabolism; D014316:Tritium
D002087:Butyrates; D038982:Integrin alpha2beta1; D020664:Son of Sevenless Proteins; D014316:Tritium; D003094:Collagen; D011392:Proline; D017526:Receptor, IGF Type 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D004150:Dipeptidases; C022449:proline dipeptidase