High glucose suppresses cathepsin activity in periodontal-ligament-derived fibroblastic cells.
The accumulation of extracellular matrices and integrins by high glucose has been reported in relation to diabetic complications. We previously reported that PDL cells expressed a higher amount of VLA-5 when cultured in high-glucose (4500 mg/L) medium than those cultured in low-glucose (1100 mg/L) medium. In this study, we aimed to address (1) whether this effect was mediated by the transcriptional level of the gene or the degradative level of the protein, and (2) whether this effect was mediated by TGF-beta. The results indicated that the level of mRNA encoding alpha5 integrin did not change in PDL cells regardless of the concentration of glucose. Alternatively, high glucose suppressed cathepsin B+L activity. Additionally, the level of mRNA encoding TGF-beta was not affected by high glucose, nor did an anti-TGF-beta neutralizing antibody have an effect on the expression of beta5 gene or cathepsin activity. Therefore, the effects of high glucose appeared to be mediated by impaired protein degradation, but not by autocrine TGF-beta.
Nishimura
F
F
Department of Periodontology and Endodontology, Okayama University Dental School, Japan.
Naruishi
K
K
Yamada
H
H
Kono
T
T
Takashiba
S
S
Murayama
Y
Y
D019898:Autocrine Communication; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D015536:Down-Regulation; D005347:Fibroblasts / Q000201:enzymology*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D006943:Hyperglycemia / Q000201:enzymology; D010513:Periodontal Ligament / Q000166:cytology / Q000201:enzymology*; D017469:Receptors, Fibronectin / Q000378:metabolism*; D018709:Statistics, Nonparametric; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism
D003470:Culture Media; D017469:Receptors, Fibronectin; D016212:Transforming Growth Factor beta; D002403:Cathepsins; D005947:Glucose