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Regulation of extracellular matrix genes by arecoline in primary gingival fibroblasts requires epithelial factors

Thangjam, GS and Agarwal, P and Balapure, AK and Rao, Girish S and Kondaiah, P (2009) Regulation of extracellular matrix genes by arecoline in primary gingival fibroblasts requires epithelial factors. In: Journal of Periodontal Research, 44 (6). pp. 736-743.

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Official URL: http://www3.interscience.wiley.com/journal/1222953...


Background and Objective: Oral submucous fibrosis, a disease of collagen disorder, has been attributed to arecoline present in the saliva of betel quid chewers. However, the molecular basis of the action of arecoline in the pathogenesis of oral submucous fibrosis is poorly understood. The basic aim of our study was to elucidate the mechanism underlying the action of arecoline on the expression of genes in oral fibroblasts. Material and Methods: Human keratinocytes (HaCaT cells) and primary human gingival fibroblasts were treated with arecoline in combination with various pathway inhibitors, and the expression of transforming growth factor-beta isoform genes and of collagen isoforms was assessed using reverse transcription polymerase chain reaction analysis. Results: We observed the induction of transforming growth factor-beta2 by arecoline in HaCaT cells and this induction was found to be caused by activation of the M-3 muscarinic acid receptor via the induction of calcium and the protein kinase C pathway. Most importantly, we showed that transforming growth factor-beta2 was significantly overexpressed in oral submucous fibrosis tissues (p = 0.008), with a median of 2.13 (n = 21) compared with 0.75 (n = 18) in normal buccal mucosal tissues. Furthermore, arecoline down-regulated the expression of collagens 1A1 and 3A1 in human primary gingival fibroblasts; however these collagens were induced by arecoline in the presence of spent medium of cultured human keratinocytes. Treatment with a transforming growth factor-beta blocker, transforming growth factor-beta1 latency-associated peptide, reversed this up-regulation of collagen, suggesting a role for profibrotic cytokines, such as transforming growth factor-beta, in the induction of collagens. Conclusion: Taken together, our data highlight the importance of arecoline-induced epithelial changes in the pathogenesis of oral submucous fibrosis.

Item Type: Journal Article
Publication: Journal of Periodontal Research
Publisher: Wiley
Additional Information: Copyright for this article belongs to Wiley.
Keywords: collagen; keratinocytes; gingival fibroblasts; transforming growth factor-beta2
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited: 07 Dec 2009 06:38
Last Modified: 19 Sep 2010 05:52
URI: http://eprints.iisc.ac.in/id/eprint/24952

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