4PBA strongly attenuates endoplasmic reticulum stress, fibrosis, and mitochondrial apoptosis markers in cyclosporine treated human gingival fibroblasts.
Study Goal
The researchers aimed to assess whether melatonin could mitigate cyclosporine-induced ER stress, matrix protein expression, and mitochondrial dysfunction in human gingival fibroblasts.
Results Summary
Melatonin significantly reduced cyclosporine-augmented ER stress markers and matrix protein expression in human gingival fibroblasts, though its effect was less pronounced than 4PBA.
Population
Human gingival fibroblasts (HGF) in vitro.
Effective Dosage
Not specified
Duration
24 hours
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
cyclosporine | increase | human gingiva | human gingiva | - | induces overgrowth | #1 |
cyclosporine | increase | ER stress | human gingival fibroblasts (HGF) | - | inducing ER stress | #2 |
cyclosporine | increase | matrix protein expression | human gingival fibroblasts (HGF) | - | increased | #3 |
cyclosporine | neutral | mitochondrial pro- and anti-apoptotic factors | human gingival fibroblasts (HGF) | - | interference with | #4 |
cyclosporine | increase | ER Stress | HGF | - | significantly augmented | #5 |
cyclosporine | increase | matrix proteins | HGF | - | significantly augmented | #6 |
melatonin | decrease | ER Stress | HGF | - | decreased significantly | #7 |
melatonin | decrease | matrix proteins | HGF | - | decreased significantly | #8 |
4PBA | decrease | ER Stress | HGF | - | decreased significantly | #9 |
4PBA | decrease | matrix proteins | HGF | - | decreased significantly | #10 |
simvastatin | decrease | ER Stress | HGF | - | decreased significantly | #11 |
simvastatin | decrease | matrix proteins | HGF | - | decreased significantly | #12 |
4PBA | decrease | cyclophilin D | HGF | - | decreased | #13 |
4PBA | decrease | Bcl2 expression | HGF | - | decreased | #14 |
4PBA | increase | cytochrome c expression | HGF | - | increase | #15 |
4PBA | neutral | effect | - | - | much more pronounced | #16 |
Cyclosporine induces overgrowth of human gingiva. Previously we have shown (i) cyclosporine-inducing ER stress in human gingival fibroblasts (HGF), (ii) increased matrix protein expression, and (iii) interference with mitochondrial pro- and anti-apoptotic factors. This study was undertaken to assess the effects of melatonin (an antioxidant), 4PBA (an ER stress inhibitor), and simvastatin on the expression of ER Stress markers as well as on matrix and mitochondrial markers. HGF incubated with cyclosporine, or without melatonin/4PBA/statin. After 24 hr of incubation, mRNA expression of ER stress markers (GRP78, CHOP, XBP1, and XBPs) and matrix protein markers (like α-SMA, VEGF, TGF-β, CTGF), and mitochondrial apoptosis markers estimated and compared with housekeeping gene GAPDH. Compared to the control cyclosporine significantly augmented ER Stress and matrix proteins, which decreased significantly with the use of melatonin, 4PBA, and simvastatin. The mitochondrial proapoptotic molecule cyclophilin D, as well as Bcl2 expression also decreased after PBA treatment, paralleling an increase in cytochrome c expression. The effect of 4PBA was much more pronounced than the influence of other two. In conclusion, 4PBA could be a viable therapeutic option for drug-induced gingival overgrowth.