4-phenylbutyric Acid Regulates Collagen Synthesis and Secretion Induced by High Concentrations of Glucose in Human Gingival Fibroblasts.
10.4196/kjpp.2011.15.6.345
- Author:
Geum Hwa LEE
1
;
Hyo Won OH
;
Hyun Dae LIM
;
Wan LEE
;
Han Jung CHAE
;
Hyung Ryong KIM
Author Information
1. Department of Dental Pharmacology and Wonkwang Dental Research Institute, School of Dentistry, Wonkwang University, Iksan 570-711, Korea. hrkimdp@wonkwang.ac.kr
- Publication Type:Original Article
- Keywords:
ER stress;
Collagen;
Human gingival fibroblasts;
Glucose;
4-PBA
- MeSH:
Activating Transcription Factor 4;
Butylamines;
Collagen;
Endoplasmic Reticulum;
Fibroblasts;
Glucose;
Humans;
Inositol;
Peptide Initiation Factors;
Phenylbutyrates;
Phosphorylation;
Transcription Factors
- From:The Korean Journal of Physiology and Pharmacology
2011;15(6):345-351
- CountryRepublic of Korea
- Language:English
-
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-1alpha) and phosphoreukaryotic initiation factor alpha (p-eIF-2alpha) was activated in the presence of high glucose. Activating transcription factor 4 (ATF-4), a downstream protein of p-eIF-2alpha 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.
