scholarly journals Egr-1 mediates low dose Arecoline induced human oral mucosa fibroblasts proliferation by transaction the expression of Wnt5a

2020 ◽  
Author(s):  
Qiang Chen ◽  
Jiuyang Jiao ◽  
Youyuan Wang ◽  
Zhihui Mai ◽  
Jing Ren ◽  
...  

Abstract Background Arecoline is the main carcinogens in Areca nut that induce oral submucous fibrosis to develop into cancer. However, many previous studies have showed that Arecoline may inhibit proliferation and prevent collagen synthesis of fibroblasts. Results High dose Arecoline (> 32 µg/ml) could inhibit but low dose Arecoline (< 16 µg/ml) could promote the proliferation of human oral fibroblasts. Wnt5a was both sufficient and necessary for the promotion of fibrobasts proliferation. Egr-1, but not NF-κB, FOXO1, Smad2 or Smad3, mediated the expression of Wnt5a in fibrobasts. The specific siRNAs of Egr-1, Egr inhibitors or Wnt5a antibodies treatment blocked Arecoline induced Wnt5a upregulation and fibroblasts proliferation. Conclusions Egr-1 mediates low dose Arecoline induced human oral mucosa fibroblasts proliferation by transaction the expression of Wnt5a, and Egr inhibitors or Wnt5a antibodies are potential therapeutic drugs of oral submucosal fibrosis and oral cancer.

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Qiang Chen ◽  
Jiuyang Jiao ◽  
Youyuan Wang ◽  
Zhihui Mai ◽  
Jing Ren ◽  
...  

Abstract Background Arecoline is an alkaloid natural product found in the areca nut that can induce oral submucous fibrosis and subsequent development of cancer. However, numerous studies have shown that arecoline may inhibit fibroblast proliferation and prevent collagen synthesis. Results High doses of arecoline (> 32 μg/ml) could inhibit human oral fibroblast proliferation, while low doses of arecoline (< 16 μg/ml) could promote the proliferation of human oral fibroblasts. Wnt5a was found to be both sufficient and necessary for the promotion of fibroblast proliferation. Egr-1 could mediate the expression of Wnt5a in fibroblasts, while NF-κB, FOXO1, Smad2, and Smad3 did not. Treatment with siRNAs specific to Egr-1, Egr inhibitors, or Wnt5a antibody treatment could all inhibit arecoline-induced Wnt5a upregulation and fibroblast proliferation. Conclusions Egr-1 mediates the effect of low dose arecoline treatment on human oral mucosa fibroblast proliferation by transactivating the expression of Wnt5a. Therefore, Egr inhibitors and Wnt5a antibodies are potential therapies for treatment of oral submucosal fibrosis and oral cancer.


Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1611
Author(s):  
Chih-Yu Peng ◽  
Yi-Wen Liao ◽  
Ming-Yi Lu ◽  
Chieh-Mei Yang ◽  
Pei-Ling Hsieh ◽  
...  

Oral submucosal fibrosis (OSF) is a premalignant disorder of the oral cavity, and areca nut chewing is known to be a major etiological factor that could induce epithelial to mesenchymal transition (EMT) and activate buccal mucosal fibroblasts (BMFs). However, this detailed mechanism is not fully understood. In this study, we showed that the upregulation of Snail in OSF samples and fibrotic BMFs (fBMFs) may result from constant irritation by arecoline, a major alkaloid of the areca nut. The elevation of Snail triggered myofibroblast transdifferentiation and was crucial to the persistent activation of fBMFs. Meanwhile, Snail increased the expression of numerous fibrosis factors (e.g., α-SMA and collagen I) as well as IL-6. Results from bioinformatics software and a luciferase-based reporter assay revealed that IL-6 was a direct target of Snail. Moreover, IL-6 in BMFs was found to further increase the expression of Snail and mediate Snail-induced myofibroblast activation. These findings suggested that there was a positive loop between Snail and IL-6 to regulate the areca nut-associated myofibroblast transdifferentiation, which implied that the blockage of Snail may serve as a favorable therapeutic strategy for OSF treatment.


Author(s):  
Shraddha Awasthi ◽  
Ausaf Ahmad ◽  
Anand Narain Srivastava

<p><strong>Introduction :</strong> oral submucosal fibrosis (OSMF) is related to juxta epithelial inflammatory response followed by a fibroelastic change of the lamina propria, with epithelial atrophy leading to stiffness of the oral mucosa, causing trismus and inability to eat.</p> <p><strong>Methods and Materials:</strong> The suitability standards for studies were: Research Articles that studied the metabolic activities in oral submucous fibrosis mainly caused by some carcinogenic substances or chemicals which may present in tobacco, alcohol, cigarettes, pan-masala etc Reference list of selected articles and reviews on the topic also were searched. studies were extracted, A total of 90-100 studies were extracted, using the keywords oral submucous fibrosis, oral potentially malignant lesion and diagnosis, collagen synthesis etc.,</p> <p><strong>Results: </strong>cancer risk among these patients, periodic biopsies of suspicious regions of the oral mucosa are essential for the early detection and management of high?risk oral premalignant lesions and prevention of cancer.</p> <p><strong>Conclusion</strong>: OSMF is hardly recognized and is poorly understood across the globe. significant improvement in management, nor reduction in its high malignant transformation rate. Better integration of medical and dental services, especially in developing countries, may reduce patients’ suffering and improve their life quality.</p>


Author(s):  
J. S. Shah ◽  
Nutan Lunagariya

Abstract Oral Submucous fibrosis (OSMF) is a chronic insidious disease of oral mucosa that occurs due to areca-nut chewing, consumption of chillies, autoimmunity and genetic predisposition. The disease starts with burning sensation and inability to tolerate spicy foods with gradual reduction in mouth opening due to fibrosis of the oral mucosa. The extension of fibrosis into the naso pharynx leads to reduction in hearing efficiency. As very few studies had been done to evaluate the hearing disability in OSMF patients, this study had been undertaken to prove the same. To evaluate hearing efficiency in patients with Oral Submucous Fibrosis of various grades of severity. Presentation includes 30 patients of osmf with various grades and evaluated for hearing efficacy by audiometry. Hearing threshold was compared in different grades of osmf. The present study revealed a significant association between OSMF and hearing deficit. Involvement of the palatal muscles with OSMF may decrease the patency of the Eustachian tube, leading to conductive hearing loss. Therefore, the protocol for managing OSMF patients should include ENT consultation and treatment for hearing deficit in order to increase the success rate of treatment.


Author(s):  
Dr. Tanoj Kumar ◽  
Anurag Rai ◽  
Dr. Minti Kumari ◽  
Dr. Shweta Rai ◽  
Dr. Avanindra Kumar ◽  
...  

Oral submucous fibrosis is a chronic progressive scarring disease of oral cavity and oropharynx characterized by epithelial atrophy and juxta epithelial inflammatory reaction with progressive fibrosis of the lamina propria and deeper connective tissue. The resulting stiffness of the oral mucosa then causes a progressive decrease in mouth opening. Hence based on above findings the present study was planned for Clinical Assessment of Occurrence of Oral Submucous Fibrosis in Patients from Patna Medical College & Hospital. The present study was planned in Department of Oral Pathology, Patna Dental College & Hospital, Patna. Total 50 cases of the patient diagnosed with the Oral Sub mucous Fibrosis (OSMF) were evaluated in the present study. History, examination and investigation of patients were done in detail as per predesigned proforma. Histopathological examination of biopsy tissue from oral mucosa was done in patients who had taken pre-therapy and post-therapy (if and when required). X-ray of temporomandibular joint was requested (whenever needed). OSMF is a commonly occurring and widely spread premalignant condition increasingly affecting the youth. The occurrence of OSMF in gutkha chewers is far faster and more severe as compared in other forms of areca nut products chewers. The easy availability and promotions of these areca nut products especially gutkha and pan masala outside the schools colleges and social places has impacted younger population in India which has led to the increased occurrence of OSMF. Keywords: Oral Submucous Fibrosis, OSFM, gutkha, pan masala, etc.


Author(s):  
Sweety Agrawal ◽  
Pratibha Deshmukh ◽  
Shweta Takalkar ◽  
Parag Sabale ◽  
Vivek Chakole

Introduction: Oral submucous fibrosis (OSMF) is a premalignant lesion of the buccal mucosa usually caused by chewing of betel nut, areca nut and tobacco. OSMF causes difficulty in laryngoscopy and intubation of the trachea. Patient of submucosal fibrosis do come for emergency and elective surgeries requiring general anaesthesia. In such scenario maintaining airway is a big challenge for anaesthesiologist. Knowledge of Prevalence of submucosal fibrosis in local region and degree of OSMF with difficult intubation may help anaesthesiologist to prepare and plan airway management in such conditions. Aims and Objectives: To evaluate the prevalence of oral submucous fibrosis in patients coming in pre-anaesthesia clinic and assessment of airway and prevalence of degree of OSMF by measuring Interincisal mouth opening in patients of oral submucosal fibrosis. Methods: Cross-sectional observational study was conducted in the department of anaesthesiology on 500 patients coming in pre-anaesthesia clinic. Patients were identified and sent to dental department for confirmation of diagnosis OSMF if one or more clinical feature of OSMF were present. A detailed proforma was used to record demographic parameter, the type of tobacco, betelnut and areccanut chewing habits, difficulty in mouth opening, inter incisor distance. OSMF was divided in 4 stages on the basis of inter incisor distance. Results: Prevalence rate of submucosal fibrosis patients coming in our pre-anaesthesia clinic was 8%. Thirty patients were found to be in stage 1 (75%.), nine patients were found to be in stage 2 (22.5%) and only one patient was in stage 3. Conclusion: Being aware of the prevalence of OSMF in the region and stages of OSMF in regard to inter incisor distance in pre-operative clinic helps anaesthesiologists to prepare and plan airway management. And hence surgical exploration can be avoided.


Author(s):  
Vishal Khandelwal ◽  
Hallaswamy V. Kambalimath ◽  
Naveen B. Reddy ◽  
Sushma Khandelwal ◽  
Vanaja Reddy ◽  
...  

Abstract A 14-year-old boy presented to our hospital with a chief complaint of difficulty in opening his mouth and a burning sensation on eating spicy food. The oral mucosa showed generalized diffused blanching and he was unable to protrude his tongue. For 6 years he had habitually chewed gutkha – a mixture of betel nut and tobacco for several minutes a day. This oral submucous fibrosis condition is very rare in young patients. The case highlights the link between oral submucous fibrosis and the regular use of areca nut (gutkha) products in a young boy.


2018 ◽  
Vol 14 (2) ◽  
pp. 60-65
Author(s):  
Ganesh Prasad Neupane ◽  
Maya Rai ◽  
R. S. Rathore ◽  
V. K. Bhargava ◽  
A. K. Mahat ◽  
...  

Introduction: Oral Submucous Fibrosis (OSMF) is a precancerous condition of the oral mucosa. It is characterized by excessive production of collagen leading to inelasticity of the oral mucosa and atrophic changes of the epithelium.Aim and objective: To evaluate the efficacy of oral Colchicine in comparison to intralesional injections of Dexamethasone plus Hyaluronidase in the management of OSMF patients.Materials and Methods: Fourty patients with OSMF were randomly divided equally into two groups. 20 patients in Dexamethasone group received biweekly intralesional injections of Dexamethasone (4mg/ml) plus Hyaluronidase 1500 IU in buccal mucosa for a period of 12 weeks. Other 20 patients in Colchicine group received oral Colchicine 0.5 mg tablets twice daily for 12 weeks. Parameters taken in the study were burning sensation, and mouth opening. Descriptive statistics, paired t test and unpaired t test were used for statistical analysis.Results and Conclusions: The pre- and post-treatment differences were found to be statistically significant for both the groups (p<0.001) and for both the treatment outcomes. When the average difference of the treatment outcomes was compared between the two study groups, statistically highly significant difference was noted (p <0.001) only in mouth opening but not in burning sensation.These encouraging results should prompt further clinical trials with Colchicine on a larger sample size to broaden the therapeutic usefulness of the drug in the management of OSMF. JNGMC,  Vol. 14 No. 2 December 2016, Page: 60-65


2020 ◽  
Vol 55 (9) ◽  
pp. 1413-1421 ◽  
Author(s):  
Chandramani B. More ◽  
Naman Rajeshkumar Rao ◽  
Sucheta More ◽  
Newell W. Johnson

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