Activation of TGF-beta Pathway by Areca Nut Constituents: A Possible Cause of Oral Submucous Fibrosis

Autor: Sivakrishna Narra, Neeraj Kumar, Imran Khan, Paturu Kondaiah, Ila Pant
Rok vydání: 2012
Předmět:
Keratinocytes
Phytochemistry
Phytochemicals
Gingiva
lcsh:Medicine
Oral Submucous Fibrosis
Smad2 Protein
Pharmacology
chemistry.chemical_compound
Oral Diseases
Transforming Growth Factor beta
Molecular Cell Biology
Nuts
Phosphorylation
lcsh:Science
Cells
Cultured
Oligonucleotide Array Sequence Analysis
Areca
Multidisciplinary
biology
Reverse Transcriptase Polymerase Chain Reaction
digestive
oral
and skin physiology
food and beverages
Genomics
Extracellular Matrix
Up-Regulation
Chemistry
Biochemistry
Medicine
Collagen
Research Article
medicine.drug
Immunology
Oral Medicine
Arecoline
Real-Time Polymerase Chain Reaction
medicine
Humans
RNA
Messenger
Biology
Inflammation
Plant Extracts
Gene Expression Profiling
lcsh:R
Immunity
Transforming growth factor beta
Molecular Reproduction
Development & Genetics (formed by the merger of DBGL and CRBME)
Fibroblasts
Arecaidine
biology.organism_classification
medicine.disease
Extracellular Matrix Composition
Plants
Toxic
Guvacine
HaCaT
chemistry
Oral submucous fibrosis
biology.protein
Mastication
Clinical Immunology
lcsh:Q
Genome Expression Analysis
Biomarkers
Transforming growth factor
Zdroj: PLoS ONE, Vol 7, Iss 12, p e51806 (2012)
PLoS ONE
Popis: Oral submucous fibrosis (OSF) is a chronic inflammatory disease characterized by the accumulation of excess collagen, and areca nut chewing has been proposed as an important etiological factor for disease manifestation. Activation of transforming growth factor-beta signaling has been postulated as the main causative event for increased collagen production in OSF. Oral epithelium plays important roles in OSF, and arecoline has been shown to induce TGF-beta in epithelial cells. In an attempt to understand the role of areca nut constituents in the manifestation of OSF, we studied the global gene expression profile in epithelial cells (HaCaT) following treatment with areca nut water extract or TGF-beta. Interestingly, 64% of the differentially regulated genes by areca nut water extract matches with the TGF-beta induced gene expression profile. Out of these, expression of 57% of genes was compromised in the presence of ALK5 (T beta RI) inhibitor and 7% were independently induced by areca nut, highlighting the importance of TGF-beta in areca nut actions. Areca nut water extract treatment induced p-SMAD2 and TGF-beta downstream targets in HaCaT cells but not in human gingival fibroblast cells (hGF), suggesting epithelial cells could be the source of TGF-beta in promoting OSF. Water extract of areca nut consists of polyphenols and alkaloids. Both polyphenol and alkaloid fractions of areca nut were able to induce TGF-beta signaling and its downstream targets. Also, SMAD-2 was phosphorylated following treatment of HaCaT cells by Catechin, Tannin and alkaloids namely Arecoline, Arecaidine and Guvacine. Moreover, both polyphenols and alkaloids induced TGF-beta 2 and THBS1 (activator of latent TGF-beta) in HaCaT cells suggesting areca nut mediated activation of p-SMAD2 involves up-regulation and activation of TGF-beta. These data suggest a major causative role for TGF-beta that is induced by areca nut in OSF progression.
Databáze: OpenAIRE
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