4-phenylbutyric Acid Regulates Collagen Synthesis and Secretion Induced by High Concentrations of Glucose in Human Gingival Fibroblasts.

The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology
Geum-Hwa LeeHyung-Ryong Kim

Abstract

High glucose leads to physio/pathological alterations in diabetes patients. We investigated collagen production in human gingival cells that were cultured in high concentrations of glucose. Collagen synthesis and secretion were increased when the cells were exposed to high concentrations of glucose. We examined endoplasmic reticulum (ER) stress response because glucose metabolism is related to ER functional status. An ER stress response including the expression of glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), inositol requiring enzyme alpha (IRE-1α) and phosphoreukaryotic initiation factor alpha (p-eIF-2α) was activated in the presence of high glucose. Activating transcription factor 4 (ATF-4), a downstream protein of p-eIF-2α as well as a transcription factor for collagen, was also phosphorylated and translocalized into the nucleus. The chemical chaperone 4-PBA inhibited the ER stress response and ATF-4 phosphorylation as well as nuclear translocation. Our results suggest that high concentrations of glucose-induced collagen are linked to ER stress and the associated phosphorylation and nuclear translocation of ATF-4.

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Citations

Nov 10, 2014·Molecular Neurobiology·Na WeiDan Liu
Feb 11, 2015·The International Journal of Biochemistry & Cell Biology·P S KolbK Ask
Jul 1, 2014·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Kihoon KimKyung-Oh Doh
Apr 9, 2013·The Journal of Biological Chemistry·Kurt A ZimmermanJoanne E Murphy-Ullrich
Apr 28, 2015·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Sunil Kumar BodaBikramjit Basu

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Methods Mentioned

BETA
protein folding
protein assay
nuclear translocation

Software Mentioned

Scion
Image
Microcal Origin

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