Browse
Submit Data
Databases
API
Help

Dataset Information

31 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effect of Lysyl Oxidase G473 A Polymorphism on Lysyl Oxidase and Total Soluble Collagen Expression in Oral Submucous Fibrosis.

ABSTRACT:

Background

Oral submucous fibrosis (OSF) is a debilitating collagen-metabolic disorder leading to submucosal fibrosis and trismus. Lysyl oxidase (LOX), a critical collagen biosynthetic enzyme, is up-regulated in OSF. Polymorphisms in the Lysyl oxidase gene have been associated with increased risk of OSF and might affect normal collagen synthesis, accumulation, or degradation, crucial in determining fibrosis severity.

Methods

One hundred OSF cases and 100 controls were genotyped for LOX G473A(Arg158Gln) polymorphism by polymerase chain reaction-restriction fragment length polymorphism. The expression of LOX was estimated both by quantitative mRNA analysis and western blot. Total soluble collagen was evaluated from mucosal tissue obtained from OSF cases. Immunohistochemical (IHC) localization of type 1 collagen was performed in mucosal tissue obtained from patients carrying various genotypes.

Results

Heterozygous G473A genotype was significantly higher in OSF cases [2.063(95% CI =1.059-4.016)], among 26-40 years age-group [4.375(95% CI=1.323-14.267),p=0.029] and in male patients [2.38 (95% CI= 1.107-5.121), p= 0.042]. LOX expression was significantly higher in cases of the heterozygous or homozygous carrier (p <0.001). We found the total soluble collagen level significantly (p <0.001) higher among patients carrying GA or AA genotype. IHC revealed focal deposition of type1 collagen in the submucosal tissue; comparatively higher deposition was evident in mucosal tissue of OSF patients carrying AA genotype.

Conclusions

These findings suggest LOX G473A polymorphism confers an increased risk of OSF and may affect collagen accumulation in OSF cases.

SUBMITTER: Mukherjee S

PROVIDER: S-EPMC8629460 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Data regarding clinical evaluation of collagen membrane in oral mucosal defects due to oral submucous fibrosis and leukoplakia.

Project description:This data depicts the clinical evaluation of collagen membrane in oral mucosal defects due to oral submucous fibrosis and leukoplakia. This data comprised of 10 patients in the age group of 20-60 (3 male and 2 female patients with grade III and grade IV oral submucous fibrosis and 5 male patients with oral leukoplakia with a size of 3-5 cm in diameter). The parameters such as pain, swelling, allergy, biodegradability of collagen membrane, degree of re-epithelisation, degree of contracture, mouth opening and wound size were assessed after the placement of collagen membrane in oral mucosal defects. There is less data regarding the usage of collagen membrane as a biological dressing material to cover mucosal defects (Rastogi et al., 2009) [1].

| S-EPMC5996286 | biostudies-literature

The Lysyl Oxidase G473A Polymorphism Exacerbates Oral Cancer Development in Humans and Mice.

Project description:Oral cancer is primarily squamous-cell carcinoma with a 5-year survival rate of approximately 50%. Lysyl oxidase (LOX) participates in collagen and elastin maturation. The propeptide of LOX is released as an 18 kDa protein (LOX-PP) in the extracellular environment by procollagen C-proteinases and has tumor-inhibitory properties. A polymorphism in the propeptide region of LOX (rs1800449, G473A) results in a single amino acid substitution of Gln for Arg. Here we investigated the frequency of rs1800449 in OSCC employing TCGA database resources and determined the kinetics and severity of precancerous oral lesion development in wildtype and corresponding knockin mice after exposure to 4-nitroquinoline oxide (4 NQO) in drinking water. Data show that the OSCC is more common in humans carrying the variant compared to the wildtype. Knockin mice are more susceptible to lesion development. The immunohistochemistry of LOX in mouse tissues and in vitro studies point to a negative feedback pathway of wildtype LOX-PP on LOX expression that is deficient in knockin mice. Data further demonstrate modulations of T cell phenotype in knockin mice toward a more tumor-permissive condition. Data provide initial evidence for rs1800449 as an oral cancer susceptibility biomarker and point to opportunities to better understand the functional mechanism of LOX-PP cancer inhibitory activity.

| S-EPMC10254048 | biostudies-literature

Targeting lysyl oxidase reduces peritoneal fibrosis.

Project description:BackgroundAbdominal surgery and disease cause persistent abdominal adhesions, pelvic pain, infertility and occasionally, bowel obstruction. Current treatments are ineffective and the aetiology is unclear, although excessive collagen deposition is a consistent feature. Lysyl oxidase (Lox) is a key enzyme required for crosslinking and deposition of insoluble collagen, so we investigated whether targeting Lox might be an approach to reduce abdominal adhesions.MethodsFemale C57Bl/6 mice were treated intraperitoneally with multiwalled carbon nanotubes (NT) to induce fibrosis, together with chemical (ß-aminoproprionitrile-BAPN) or miRNA Lox inhibitors, progesterone or dexamethasone. Fibrotic lesions on the diaphragm, and expression of fibrosis-related genes in abdominal wall peritoneal mesothelial cells (PMC) were measured. Effects of BAPN and dexamethasone on collagen fibre alignment were observed by TEM. Isolated PMC were cultured with interleukin-1 alpha (IL-1α) and progesterone to determine effects on Lox mRNA in vitro.ResultsNT-induced fibrosis and collagen deposition on the diaphragm was ameliorated by BAPN, Lox miRNA, or steroids. BAPN and dexamethasone disrupted collagen fibres. NT increased PMC Lox, Col1a1, Col3a1 and Bmp1 mRNA, which was inhibited by steroids. Progesterone significantly inhibited IL-1α induced Lox expression by PMC in vitro.ConclusionOur results provide proof-of-concept that targeting peritoneal Lox could be an effective approach in ameliorating fibrosis and adhesion development.

| S-EPMC5553776 | biostudies-literature

Proposed clinical definition for oral submucous fibrosis.

Project description:Oral Submucous Fibrosis (OSMF) is an insidious, chronic, complex, crippling, debilitating, irreversible, progressive, scarring, potentially malignant and collagen metabolic disorder, induced by a known carcinogen areca nut; wherein the oral mucosa, and occasionally the pharynx and esophagus is subjected to various pathological changes with significant clinical manifestations at different stages of progression, leading to functional morbidity; and with a risk of malignant transformation in the overlying epithelium. Although the condition is mainly diagnosed based on classic clinical manifestations, the commonly used existing definition for oral submucous fibrosis is primarily based on histological features. The authors have conducted extensive clinical research studies on OSMF and intends to propose a new clinical definition as 'a debilitating, progressive, irreversible collagen metabolic disorder induced by chronic chewing of areca nut and its commercial preparations; affecting the oral mucosa and occasionally the pharynx and esophagus; leading to mucosal stiffness and functional morbidity; and has a potential risk of malignant transformation.' Thus, a new clinical definition is put forward so as to assist the academicians, researchers and clinicians in terming and grouping this disease according to its clinical and biological behaviour for its subsequent management.

| S-EPMC6614531 | biostudies-literature

Drug treatment for oral submucous fibrosis: an update.

Project description:ObjectiveThe aim of this review is to evaluate the different medicinal interventions available for the management of oral submucous fibrosis (OSF).Materials and methodsWe conducted a comprehensive electronic search on PubMed, Web of Science, and Cochrane Library databases for articles related to OSF patients treated with medications from December 2011 to September 2022. GRADE system was used to evaluate the evidence quality. The reporting of the systematic review is in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The main outcomes were the improvement of maximum mouth opening, burning sensation, cheek flexibility, and tongue protrusion.ResultsTwenty-nine randomized controlled trials (RCTs), five clinical trials (CCTs) were included, and the use of drugs for OSF treatment were evaluated. Drugs like steroids, hyaluronidase, pentoxifylline, lycopene, curcumin, dpirulina, aloe vera, omega3, oxitard, allicin, colchicine have been used. It was found that drugs with evidence high quality were salvia miltiorrhiza combined with triamcinolone acetonide, lycopene, pentoxifylline, curcumin, and aloe vera, and those with evidence moderate quality were allicin, colchicine, omega 3, and oxitard.ConclusionBased on the results of our comprehensive analysis, for long-term treatment, we found lycopene with low side effects, whereas for relieving the symptoms of severe burning sensation, aloe vera is the most effective. Although the recent review has made some progress, drug therapy for OSF remains unclear, and more high-quality RCTs are needed to identify better treatments for OSF.

| S-EPMC10568776 | biostudies-literature

Polyphenol-based targeted therapy for oral submucous fibrosis.

Project description:Oral submucous fibrosis (OSF) is a chronic, progressive, and precancerous condition mainly caused by chewing areca nut. Currently, OSF therapy includes intralesional injection of corticosteroids with limited therapeutic success in disease management. Therefore, a combined approach of in silico, in vitro and in vivo drug development can be helpful. Polyphenols are relatively safer than other synthetic counterparts. We used selected polyphenols to shortlist the most suitable compound by in silico tools. Based on the in silico results, epigallocatechin-3-gallate (EGCG), quercetin (QUR), resveratrol, and curcumin had higher affinity and stability with the selected protein targets, transforming growth factor beta-1 (TGF-β1), and lysyl oxidase (LOX). The efficacy of selected polyphenols was studied in primary buccal mucosal fibroblasts followed by in vivo areca nut extract induced rat OSF model. In in vitro studies, the induced fibroblast cells were treated with EGCG and QUR. EGCG was safer at higher concentrations and more efficient in reducing TGF-β1, collagen type-1A2 and type-3A1 mRNA expression than QUR. In vivo studies confirmed that the EGCG hydrogel was efficient in improving the disease conditions compared to the standard treatment betamethasone injection with significant reduction in TGF-β1 and collagen concentrations with increase in mouth opening. EGCG can be considered as a potential, safer and efficient phytomolecule for OSF therapy and its mucoadhesive topical formulation help in the improvement of patient compliance without any side effects. Highlights Potential polyphenols were shortlisted to treat oral submucous fibrosis (OSF) using in silico tools Epigallocatechin 3-gallate (EGCG) significantly reduced TGF-β1 and collagen both in vitro and in vivo EGCG hydrogel enhanced antioxidant defense, modulated inflammation by reducing TGF-β1 and improved mouth opening in OSF rat model.

| S-EPMC10518296 | biostudies-literature

Effect of lysyl oxidase (LOX) on corpus cavernous fibrosis caused by ischaemic priapism.

Project description:Penile fibrosis caused by ischemic priapism (IP) adversely affects patients' erectile function. We explored the role of lysyl oxidase (LOX) in rat and human penes after ischemic priapism (IP) to verify the effects of anti-LOX in relieving penile fibrosis and preventing erectile dysfunction caused by IP in rats. Seventy-two rats were randomly divided into six groups: control group, control + ?-aminopropionitrile (BAPN) group, 9 hrs group, 9 hrs + BAPN group, 24 hrs group, and 24 hrs + BAPN group. ?-aminopropionitrile (BAPN), a specific inhibitor of LOX, was administered in the drinking water. At 1 week and 4 weeks, half of the rats in each group were randomly selected for the experiment. Compared to the control group, the erectile function of IP rats was significantly decreased while the expression of LOX in the corpus cavernosum was significantly up-regulated in both 9 and 24 hrs group. Proliferated fibroblasts, decreased corpus cavernosum smooth muscle cells/collagen ratios, destroyed endothelial continuity, deposited abnormal collagen and disorganized fibers were observed in IP rats. The relative content of collage I and III was not obviously different among the groups. ?-aminopropionitrile (BAPN) could effectively improve the structure and erectile function of the penis, and enhance recovery. The data in this study suggests that LOX may play an important role in the fibrosis of corpus cavernosum after IP and anti-LOX may be a novel target for patients suffering with IP.

| S-EPMC5824375 | biostudies-literature

p53 polymorphism and association of human papillomavirus in oral submucous fibrosis and oral squamous cell carcinoma: A case-control study.

Project description:IntroductionThe tumor-suppressor p53 protein is inactivated by the human papillomavirus (HPV) E6 oncoprotein, causing polymorphism of the p53 at codon 72 of exon either proline (Pro) or arginine (Arg). Specific allele predisposition has been reported in the literature. The association between the p53 allele and HPV types has been reported. We analyzed the association between p53 polymorphism at codon 72 and HPV 16 and 18 genotypes in control, oral submucous fibrosis (OSF) and oral squamous cell carcinoma (OSCC).Materials and methodsOf the total 90 cases, biopsy tissues of all groups (30 cases of OSF, OSCC and control each) were collected to extract DNA. Polymerase chain reaction was used to detect HPV 16 and 18 and alleles of codon 72 in p53 were evaluated in all the samples.ResultsIn control, OSF and OSCC samples showed the presence HPV 63.3%, 33.3% and 60%, respectively. In OSF, HPV 16 and 18 was detected in four and four cases, respectively, whereas in OSCC, HPV 16 and 18 was detected in ten and nine cases, respectively. In all three groups, predominantly, Arg/Arg protein was present followed by Pro/Pro and Arg/Pro. Among the control, Arg/Arg type protein was frequently seen followed by Arg/Pro, Pro/Pro in the presence of HPV. OSF and OSCC were associated homologous genes in the presence of HPV.ConclusionThe definite association between p53 codon 72, polymorphism and HPV 16 and 18 was seen in OSCC with low frequency in OSF. Frequency of homozygous genotype is at high risk in the presence of HPV 16 and 18 in developing OSCC.

| S-EPMC6503778 | biostudies-literature

Serum Lysyl Oxidase Levels and Lysyl Oxidase Gene Polymorphism in Ovarian Cancer Patients of Eastern Indian Population.

Project description:(1) Background: Lysyl oxidase (LOX) plays a dual role in carcinogenesis and studies show a higher risk of cancer in LOX G473A variants. The present study evaluated the pattern of LOX G473A polymorphism (rs1800449) and serum LOX levels in ovarian cancer patients. (2) Methods: Serum LOX levels were estimated by enzyme linked immunosorbent assay (ELISA). A polymorphism of rs1800449 of LOX gene was detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Selected samples were sequenced for external validation. (3) Results: A majority of study participants were from low socio-economic status. Serum LOX level was significantly higher in ovarian cancer patients as compared to control. Serum LOX level in early-stage ovarian cancer was significantly lower as compared to advanced stage (FIGO stage III & IV). Wild type GG genotype was used as reference. Genotypes AA were associated with a significant risk of epithelial ovarian cancer (OR 3.208; p value- 0.033). A allele of rs1800449 polymorphism of LOX gene, the odds ratio was 1.866 (95% Confidence Interval 1.112-3.16) p value = 0.017 (4) Conclusions: A allele of rs1800449 polymorphism of LOX gene presents an increased risk of ovarian cancer in East Indian population. Serum LOX levels could be a potential biomarker for the diagnosis and prognosis of ovarian cancer.

| S-EPMC8774920 | biostudies-literature

Stromal thrombospondin 1 suppresses angiogenesis in oral submucous fibrosis.

Project description:A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis (OSF), a premalignant disease that is largely induced by betel quid chewing. However, the lack of available models has challenged studies of angiogenesis in OSF. Here, we found that the expression of thrombospondin 1 (THBS1), an endogenous angiostatic protein, was elevated in the stroma of tissues with OSF. Using a fibroblast-attached organoid (FAO) model, the overexpression of THBS1 in OSF was stably recapitulated in vitro. In the FAO model, treatment with arecoline, a major pathogenic component in areca nuts, enhanced the secretion of transforming growth factor (TGF)-β1 by epithelial cells, which then promoted the expression of THBS1 in fibroblasts. Furthermore, human umbilical vein endothelial cells (HUVECs) were incorporated into the FAO to mimic the vascularized component. Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs (vFAOs). Consistently, treatment with arecoline reduced the expression of CD31 in vFAOs, and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36, a receptor of THBS1. Finally, in an arecoline-induced rat OSF model, THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo. Overall, we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.

| S-EPMC10894862 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data