Zoledronic acid impairs re-epithelialization through down-regulation of integrin αvβ6 and transforming growth factor beta signalling in a three-dimensional in vitro wound healing model

Abstract Background Curcumin accelerates healing of oral wounds; however, the responsible mechanisms remain underexplored. Our hypothesis is curcumin regulates the expression of wound healing-related genes in human gingival fibroblasts (hGFs). This study investigated whether curcumin regulates transforming growth factor (TGF)-β1, type I TGF-β receptor (TGF-βRI), type II TGF-β receptor (TGF-βRII), and vascular endothelial growth factor (VEGF) expression in unwounded hGFs and an in vitro hGF wound healing model. Methods The cytotoxicity of curcumin was evaluated using the MTT assay. Unwounded hGFs were treated with non-cytotoxic concentrations of curcumin for 24 h. Gene expression was determined by quantitative polymerase chain reaction. Then, hGFs were treated with 1 µM curcumin in an in vitro wound healing model. PD98059 pretreatment was performed to determine whether extracellular signal-regulated kinase (ERK) signaling was required for regulation of gene expression by curcumin. Results Curcumin at 0.1–20 µM caused no significant change in cell viability. In unwounded hGFs, curcumin had no significant effect on TGF-β1, TGF-βRI, TGF-βRII, or VEGF expression. Conversely, curcumin significantly upregulated the expression of these genes in the in vitro wound healing model. PD98059 significantly attenuated the curcumin-stimulated TGF-βRI, TGF-βRII, and VEGF expression, whereas it had no effect on TGF-β1 expression. Conclusions Curcumin upregulated TGF-β1, TGF-βRI, TGF-βRII, and VEGF expression in an in vitro hGF wound healing model. The ERK pathway is required for TGF-βRI, TGF-βRII, and VEGF induction by curcumin. Our findings support the development of curcumin as a therapeutic agent for gingival ulcers.

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Salivary EGF regulates eosinophil-derived TGF-alpha expression in hamster oral wounds

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1996.270.1.g191 ◽

1996 ◽

Vol 270 (1) ◽

pp. G191-G202 ◽

Cited By ~ 2

Author(s):

J. Yang ◽

L. W. Tyler ◽

R. B. Donoff ◽

B. Song ◽

A. J. Torio ◽

...

Keyword(s):

Wound Healing ◽

Growth Factor ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Tgf Beta ◽

Epidermal Growth ◽

Factor Alpha ◽

Wound Healing Model ◽

Oral Wound Healing ◽

Healing Model

Using hamster as an oral wound healing model, we examined eosinophils and their expression of transforming growth factor-alpha (TGF-alpha) and transforming growth factor-beta 1 (TGF-beta 1). Oral wounds healed approximately two times faster than their cutaneous counterparts. Eosinophils infiltrated prominently into oral wounds; however, unlike the dual expression of TGF-alpha and TGF-beta 1 in skin wounds, oral wound-associated eosinophils expressed TGF-beta 1, but not TGF-alpha. Because saliva is present in oral environments and contains epidermal growth factor (EGF) and TGF-alpha, sialoadenectomy was performed in this model to determine whether the lack of TGF-alpha expression by eosinophils in oral wounds is due to the presence of salivary EGF and/or TGF-alpha. We found that eosinophils in sialoadenectomized hamsters did express TGF-alpha during oral wound healing but that such expression was suppressed when EGF was added to their drinking water. Taken together, our findings suggest that eosinophil-derived TGF-alpha and salivary TGF-alpha/ EGF may have complementary roles in contributing to TGF-alpha in oral wound healing.

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