Quantitative disease resistance in wild Silene vulgaris to its endemic pathogen Microbotryum silenes-inflatae.

The evolution of disease resistances is an expected feature of plant-pathogen systems, but whether the genetics of this trait most often produces qualitative or quantitative phenotypic variation is a significant gap in our understanding of natural populations. These two forms of resistance variation are often associated with differences in number of underlying loci, the specificities of host-pathogen coevolution, as well as contrasting mechanisms of preventing or slowing the infection process. Anther-smut disease is a commonly studied model for disease of wild species, where infection has severe fitness impacts, and prior studies have suggested resistance variation in several host species. However, because the outcome of exposing the individual host to this pathogen is binary (healthy or diseased), resistance has been previously measured at the family level, as the proportion of siblings that become diseased. This leaves uncertain whether among-family variation reflects contrasting ratios of segregating discrete phenotypes or continuous trait variation among individuals. In the host Silene vulgaris, plants were replicated by vegetative propagation in order to quantify the infection rates of the individual genotype with the endemic anther-smut pathogen, Microbotryum silenes-inflatae. The variance among field-collected families for disease resistance was significant, while there was unimodal continuous variation in resistance among genotypes. Using crosses between genotypes within ranked resistance quartiles, the offspring infection rate was predicted by the parental resistance values. While the potential remains in this system for resistance genes having major effects, as there were suggestions of such qualitative resistance in a prior study, here the quantitative disease resistance to the endemic anther-smut pathogen is indicated for S. vulgaris. The variation in natural populations and strong heritability of the trait, combined with severe fitness consequences of anther-smut disease, suggests that resistance in these host populations is highly capable of responding to disease-induced selection.

Incidence disparities of obstructive sleep apnea-associated lung cancer by gender; Korean National Health Insurance data analysis.

Introduction: Obstructive sleep apnea (OSA) is known to increase the risk of various cancers. By analyzing the Korea National Health Insurance Service (KNHIS) registry, the impact of OSA on the lung cancer incidence was analyzed in a retrospective cohort group. Methods: A retrospective cohort of adult patients newly registered with OSA in the KNHIS data from 2007 to 2017 was included and observed until December 2019 (12 years). The main outcome measure was newly diagnosed lung cancer. The control group was set with age and sex that matched those in the OSA group. Results: The hazard ratio (HR) of OSA for lung cancer incidence showed a significantly reduced HR of 0.87 (95% CI, 0.82-0.93). The observed significance of this finding was limited to male OSA patients [HR, 0.84 (95% CI, 0.78-0.90)], while no significant association was found in female OSA patients [HR, 1.05 (95% CI, 0.91-1.21)], irrespective of their age. Discussion: OSA patients have a lower risk of developing lung cancer, but this risk reduction is gender-specific, as female OSA patients do not show a reduction in hazard ratio.

Limited Palatal Muscle Resection for the Treatment of Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis.

Background and Objectives: Limited palatal muscle resection (PMR) is a surgical technique employed to alleviate respiratory disturbances in obstructive sleep apnea (OSA) patients with retropalatal narrowing by reducing soft palate volume and tightening the muscles. Although some previous publications have demonstrated the effectiveness of limited PMR, the overall efficacy and therapeutic role of limited PMR for the treatment of OSA remain uncertain. This study utilized meta-analysis and a systematic literature review to estimate the overall effectiveness of limited PMR in treating OSA. Materials and Methods: Multiple databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, were searched using specific keywords related to OSA and limited PMR. Original articles assessing respiratory disturbances before and after limited PMR in patients with OSA were included. Data from selected articles were collected using standardized forms, including clinicodemographic characteristics, apnea-hypopnea index (AHI), and lowest pulse oximetry values (minimum SpO2). Random effect models were used for analyzing significant heterogeneity. Egger's test and funnel plot were used to identify publication bias. Results: Four studies were included in this meta-analysis for AHI, and three studies were included for minimum SpO2 during sleep. A significant reduction in the AHI and an increase in the minimum SpO2 were shown following limited PMR as the standardized mean difference (95% confidence interval) was 2.591 (1.092-4.090) and 1.217 (0.248-2.186), respectively. No publication bias was found in either analysis. Conclusions: The results of the meta-analysis and systemic review add to the literature that limited PMR can result in a reduction in the AHI and an increase in min SaO2. In OSA patients with suspected retropalatal obstruction, limited PMR may be efficiently performed.

Testicular Cancer Incidence among Obstructive Sleep Apnea (OSA) Patients: South Korean National Health Insurance Data.

Obstructive sleep apnea (OSA) has been linked to an increased risk of acquiring many types of cancer. No data on the prevalence of testicular cancer in OSA patients have been reported in the literature. The goal of the present investigation is to find out the impact of OSA on the incidence of testicular cancer based on the Korea National Health Insurance Service (KNHIS) dataset. A cohort of adult male patients newly registered with OSA in the KNHIS data from 2007 to 2014 who had no history of any previous cancer diagnosis was included. The main outcome measure was newly diagnosed testicular cancer in the National Medical Expenses Support Program. The control group was set at five times larger than the OSA group, and it was matched with age and sex. The cumulative incidence and hazard ratio (HR) for the development of testicular cancer were compared between the OSA and control groups. Further subgroup analysis was conducted in the three different age groups. In the study period, a total of 152,801 male adult patients newly diagnosed with OSA were included, whereas 764,005 individuals were recruited as the control group. The HR of OSA for developing testicular cancer was 1.58 (95% confidence interval [CI]: 0.92-2.60), showing no significant HR regardless of confounding adjustment. However, the subgroup analysis revealed a significantly increased HR to develop testicular cancer of 3.39 (95% CI: 1.08-10.06) in groups aged more than 65, whereas the age ranges of 20-40 and 40-64 showed no significance (1.19 (0.44-2.75) and 1.27 (0.50-2.80), respectively). OSA may not influence the incidence of testicular cancer in the general adult population. However, compared to younger males, males over 65 may be more susceptible to OSA when it comes to developing testicular cancer.

Estimation of the Effectiveness of a Tighter, Reinforced Quarantine for the Coronavirus Disease 2019 (COVID-19) Outbreak: Analysis of the Third Wave in South Korea.

It has been claimed that a tighter, reinforced quarantine strategy was advocated to reduce the transmission of coronavirus disease 2019 (COVID-19) during major outbreaks; however, there have been no prior quantitative studies examining the effectiveness and duration of such a reinforced quarantine. Consequently, the purpose of this research was to determine the impact of a "tighter, reinforced" quarantine during the third COVID-19 breakout wave in South Korea, which occurred between late 2020 and early 2021. The efficacy of the quarantine was determined by comparing the number of newly diagnosed COVID-19 patients between the "prediction model" and "actual observed data." Two prediction models were developed using the autoregressive integrated moving average (ARIMA; 1, 0, 0) model. The effect of a "tighter, reinforced" quarantine, which would show as an immediate drop in the number of new cases, predicted its efficacy by lowering the number of new cases by 20,400. In addition, the efficacy of the quarantine lasted up to more than three months. The findings of our investigation confirmed the beneficial influence of "tighter, controlled" quarantine laws during a widespread COVID-19 epidemic. During an epidemic, when the population has not yet developed immunity to respiratory viral diseases, our study may be evidence for implementing stricter quarantine restrictions in order to reduce the number of new cases.

Clinical Practice Guideline: Clinical Efficacy of Nasal Surgery in the Treatment of Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is a common disorder characterized by upper airway obstruction during sleep. To reduce the morbidity of OSA, sleep specialists have explored various methods of managing the condition, including manifold positive airway pressure (PAP) techniques and surgical procedures. Nasal obstruction can cause significant discomfort during sleep, and it is likely that improving nasal obstruction would enhance the quality of life and PAP compliance of OSA patients. Many reliable studies have offered evidence to support this assumption. However, few comprehensive guidelines for managing OSA through nasal surgery encompass all this evidence. In order to address this gap, the Korean Society of Otorhinolaryngology-Head and Neck Surgery (KORL-HNS) and the Korean Society of Sleep and Breathing designated a guideline development group (GDG) to develop recommendations for nasal surgery in OSA patients. Several databases, including OVID Medline, Embase, the Cochrane Library, and KoreaMed, were searched to identify all relevant papers using a predefined search strategy. The types of nasal surgery included septoplasty, turbinate surgery, nasal valve surgery, septorhinoplasty, and endoscopic sinus surgery. When insufficient evidence was found, the GDG sought expert opinions and attempted to fill the evidence gap. Evidence-based recommendations for practice were ranked according to the American College of Physicians' grading system. The GDG developed 10 key action statements with supporting text to support them. Three statements are ranked as strong recommendations, three are only recommendations, and four can be considered options. The GDG hopes that this clinical practice guideline will help physicians make optimal decisions when caring for OSA patients. Conversely, the statements in this guideline are not intended to limit or restrict physicians' care based on their experience and assessment of individual patients.

Comparison of body size perception of young women in Korea and the United States.

Body size perception among young women in Asian and Western countries is believed to be quite different, however, there are no confirming studies. We analyzed the data from young women aged between 20 and 40 who participated in the National Health and Nutrition Examination Survey (2001-2018) of the United States (US) and Korea. US young women had higher rates of being overweight and obesity than Korean young women, and there was no significant change over 20 years. In both countries, the percentage of properly estimating one's own weight exceeded 70 percent and remained relatively steady. The percentage of overestimating one's own weight was only about 10 percent in Korea in 2001, but increased to 20 percent. In the case of the US, the percentage was about 15 percent in 2001-2002, but has since continued to decline. The percentage of underestimating one's own body weight was about 18 percent in Korea in 2001, but decreased to about 8 percent. In the case of the US, the percentage was very low at about 10 percent in 2001-2002, but gradually increased to about 18 percent in 2017-2018. In conclusion, young women in the US tend to underestimate their body size, and those in Korea tend to overestimate it.

Tailored antiplatelet therapy in stent assisted coiling for unruptured aneurysms: a nationwide registry study.

BACKGROUND: Antiplatelet therapy, where regimens are tailored based on platelet function testing, has been introduced into neurointerventional surgery. This nationwide registry study evaluated the effect and safety of tailored antiplatelet therapy in stent assisted coiling for unruptured aneurysms compared with conventional therapy using a standard regimen. METHODS: This study enrolled 1686 patients in 44 participating centers who received stent assisted coiling for unruptured aneurysms between January 1, 2019 and December 31, 2019. The standard regimen (aspirin and clopidogrel) was used for all patients in the conventional group (924, 19 centers). The regimen was selected based on platelet function testing (standard regimen for clopidogrel responders; adding cilostazol or replacing clopidogrel with other thienopyridines (ticlopidine, prasugrel, or ticagrelor) for clopidogrel non-responders) in the tailored group (762, 25 centers). The primary outcome was thromboembolic events. Secondary outcomes were bleeding and poor outcomes (increase in modified Rankin Scale score). Outcomes within 30 days after coiling were compared using logistic regression analysis. RESULTS: The thromboembolic event rate was lower in the tailored group than in the conventional group (30/762 (3.9%) vs 63/924 (6.8%), adjusted OR 0.560, 95% CI 0.359 to 0.875, P=0.001). The bleeding event rate was not different between the study groups (62/762 (8.1%) vs 73/924 (7.9%), adjusted OR 0.790, 95% CI 0.469 to 1.331, P=0.376). Poor outcomes were less frequent in the tailored group (12/762 (1.6%) vs 34 (3.7%), adjusted OR 0.252, 95% CI 0.112 to 0.568, P=0.001). CONCLUSION: Tailored antiplatelet therapy in stent assisted coiling for unruptured aneurysms reduced thromboembolic events and poor outcomes without increasing bleeding.

The Effect of Pharyngeal Surgery on Positive Airway Pressure Therapy in Obstructive Sleep Apnea: A Meta-Analysis.

There is controversy about the effect of pharyngeal surgery for obstructive sleep apnea (OSA) on positive airway pressure (PAP) adherence, and the related results of meta-analysis have not yet been available. Therefore, the purpose of this meta-analysis was to assess the effect of pharyngeal OSA surgery on PAP therapy parameters such as optimal pressure levels and usage time. We selected studies investigating optimal PAP levels or usage time before and after pharyngeal OSA surgery, regardless of the study design. Pharyngeal OSA surgery included uvulopalatopharyngoplasty and its variants, tonsillectomy, Pillar implants, radiofrequency ablation, tongue base surgery and its variants, and genioglossus advancement. Studies in which isolated nasal surgery was performed were excluded. The random-effects model was used due to significant heterogeneity among the studies. Nine studies were included in the meta-analysis of optimal PAP levels, and five studies in the meta-analysis of PAP usage time. After pharyngeal OSA surgery, the summed optimal PAP level was significantly decreased (standardized mean difference (SMD), -1.113; 95% confidence interval (CI), -1.667 to -0.559)), and the summed usage time of PAP was significantly increased (SMD, 0.794; 95% CI, 0.259 to 1.329). This study illustrated that pharyngeal OSA surgery lowered optimal PAP levels and enhanced PAP usage time. The results of the meta-analysis contribute to our understanding of the role of pharyngeal OSA surgery in patients with PAP intolerance.

Can disease resistance evolve independently at different ages? Genetic variation in age-dependent resistance to disease in three wild plant species.

Juveniles are typically less resistant (more susceptible) to infectious disease than adults, and this difference in susceptibility can help fuel the spread of pathogens in age-structured populations. However, evolutionary explanations for this variation in resistance across age remain to be tested.One hypothesis is that natural selection has optimized resistance to peak at ages where disease exposure is greatest. A central assumption of this hypothesis is that hosts have the capacity to evolve resistance independently at different ages. This would mean that host populations have (a) standing genetic variation in resistance at both juvenile and adult stages, and (b) that this variation is not strongly correlated between age classes so that selection acting at one age does not produce a correlated response at the other age.Here we evaluated the capacity of three wild plant species (Silene latifolia, S. vulgaris and Dianthus pavonius) to evolve resistance to their anther-smut pathogens (Microbotryum fungi), independently at different ages. The pathogen is pollinator transmitted, and thus exposure risk is considered to be highest at the adult flowering stage.Within each species we grew families to different ages, inoculated individuals with anther smut, and evaluated the effects of age, family and their interaction on infection.In two of the plant species, S. latifolia and D. pavonius, resistance to smut at the juvenile stage was not correlated with resistance to smut at the adult stage. In all three species, we show there are significant age × family interaction effects, indicating that age specificity of resistance varies among the plant families. Synthesis. These results indicate that different mechanisms likely underlie resistance at juvenile and adult stages and support the hypothesis that resistance can evolve independently in response to differing selection pressures as hosts age. Taken together our results provide new insight into the structure of genetic variation in age-dependent resistance in three well-studied wild host-pathogen systems.

Validation Study on Automated Sleep Stage Scoring Using a Deep Learning Algorithm.

Background and Objectives: Polysomnography is manually scored by sleep experts. However, manual scoring is a time-consuming and labor-intensive task. The goal of this study was to verify the accuracy of automated sleep-stage scoring based on a deep learning algorithm compared to manual sleep-stage scoring. Materials and Methods: A total of 602 polysomnography datasets from subjects (Male:Female = 397:205) aged 19 to 65 years (mean age, 43.8, standard deviation = 12.2) were included in the study. The performance of the proposed model was evaluated based on kappa value and bootstrapped point-estimate of median percent agreement with a 95% bootstrap confidence interval and R = 1000. The proposed model was trained using 482 datasets and validated using 48 datasets. For testing, 72 datasets were selected randomly. Results: The proposed model exhibited good concordance rates with manual scoring for stages W (94%), N1 (83.9%), N2 (89%), N3 (92%), and R (93%). The average kappa value was 0.84. For the bootstrap method, high overall agreement between the automated deep learning algorithm and manual scoring was observed in stages W (98%), N1 (94%), N2 (92%), N3 (99%), and R (98%) and total (96%). Conclusions: Automated sleep-stage scoring using the proposed model may be a reliable method for sleep-stage classification.

Increased incidence of leukemia in patients with obstructive sleep apnea: Results from the national insurance claim data 2007-2014.

PURPOSE: Prior research suggests a link between obstructive sleep apnea (OSA) and the likelihood of developing a variety of solid tumors; however, there are no studies assessing OSA and leukemia. This study is the first to identify a potential association between OSA and leukemia using data from the Korea National Health Insurance Service database. METHODS: A total of 162,646 patients (≥20 years of age and without any cancer history) newly diagnosed with OSA between 2011 and 2017 were included. A control group of 813,230 subjects was selected using propensity score matching based on age and sex. The mean follow-up time was 4.4 ± 2.0 years. The primary endpoint was newly diagnosed leukemia of any type. The leukemia hazard ratio (95% confidence interval [CI]) was calculated for patients with OSA and compared with that of patients in the control group. RESULTS: The incidence of leukemia among patients with OSA was significantly higher than that in the controls (1.35 [1.05-1.74]). The hazard ratio was the highest, 1.74 in those under 40 years, and gradually decreased with age, to 1.38 in those aged 40-65 years and 0.96 in those over 65. In particular, the incidence of lymphoid leukemia (2.06 [1.18-3.60]) was higher than that of myeloid (1.34 [1.00-1.81]) or unspecified leukemia (0.60 [0.20-1.58]). CONCLUSION: OSA is associated with an increased incidence of leukemia, particularly in patients younger than 40 years of age.

Aeroallergen Sensitization Status in South Korea From 2018 to 2021.

OBJECTIVES: Studies on the aeroallergen sensitization status of South Koreans based on large-scale data are lacking. METHODS: We analyzed data from 368,156 multiple allergosorbent tests collected by a domestic medical diagnosis company from 3,735 hospitals nationwide from 2018 to 2021. We additionally collected sex, age, and regional data. If the level of an aeroallergen was 0.35 IU/mL or more, the test result for that aeroallergen was defined as positive, and positive cases were defined as those where one aeroallergen was positive. The positive ratio (PR) for aeroallergens was calculated using positive cases. RESULTS: In total, 347,996 cases were analyzed, excluding cases with missing data. The percentage of positive cases was 56.7%, which was highest in adolescents (74.1%) and lowest in the elderly (47.0%). All four types of mites had high PRs (0.382-0.655), and mold had low PRs (0.023-0.058). Among pollens, the PRs of grasses were generally high (more than 0.14), followed by weeds (approximately 0.10), and the PRs of woods was less than 0.1. For animals, cats and dogs had the highest PRs, at 0.231 and 0.183, respectively. The value for cockroaches was also high, at 0.211. The PRs of indoor aeroallergens, such as mites, molds, and animals, were high in adolescents, and those of pollen and cockroaches were high in the elderly. In Jeju, the PR of Japanese cedars was extremely high (0.222). CONCLUSION: Koreans were found to be sensitized to a wide variety of aeroallergens. There were significant differences in sensitization patterns according to age and region.

Angiographic characteristics of ruptured versus unruptured vertebral artery dissecting aneurysm.

OBJECTIVE: Vertebral artery dissecting aneurysm (VADA) is a rare and critical disease. VADA rupture can cause subarachnoid hemorrhage which is a major complication of VADA due to their high rebleeding rate and poor outcome. In the present study, ruptured and unruptured VADAs were compared by analyzing angiographic findings to determine useful predisposing factors for VADA rupture for appropriate treatment selection. METHODS: Subjects with VADA treated during a 10-year period were retrospectively identified. The 57 cases diagnosed with VADA were divided into ruptured (n=15) and unruptured (n=42) groups. In addition, each case was analyzed using angiographic 3-dimensional (3-D) reconstructed images. Factors such as length, dilated and stenotic diameter, shape, and vessel around the vertebral artery (VA) were measured and statistically compared. RESULTS: In the ruptured group, stenotic findings of the affected lesion were more common and severe than in the unruptured group. The average stenotic diameter was 2.27 mm (vs. 2.84 mm). And stenotic degree was 62% and 53% in the ruptured and unruptured groups, respectively. Posterior communicating artery (PcomA) flow was more common in the ruptured group (87% vs. 55%, p=0.028). Conclusions: Based on angiographic findings, stenotic lesions, which may be influenced by PcomA flow, are more common in ruptured VADAs.

Interrater reliability of sleep stage scoring: a meta-analysis.

STUDY OBJECTIVES: We evaluated the interrater reliabilities of manual polysomnography sleep stage scoring. We included all studies that employed Rechtschaffen and Kales rules or American Academy of Sleep Medicine standards. We sought the overall degree of agreement and those for each stage. METHODS: The keywords were "Polysomnography (PSG)," "sleep staging," "Rechtschaffen and Kales (R&K)," "American Academy of Sleep Medicine (AASM)," "interrater (interscorer) reliability," and "Cohen's kappa." We searched PubMed, OVID Medline, EMBASE, the Cochrane library, KoreaMed, KISS, and the MedRIC. The exclusion criteria included automatic scoring and pediatric patients. We collected data on scorer histories, scoring rules, numbers of epochs scored, and the underlying diseases of the patients. RESULTS: A total of 101 publications were retrieved; 11 satisfied the selection criteria. The Cohen's kappa for manual, overall sleep scoring was 0.76, indicating substantial agreement (95% confidence interval, 0.71-0.81; P < .001). By sleep stage, the figures were 0.70, 0.24, 0.57, 0.57, and 0.69 for the W, N1, N2, N3, and R stages, respectively. The interrater reliabilities for stage N2 and N3 sleep were moderate, and that for stage N1 sleep was only fair. CONCLUSIONS: We conducted a meta-analysis to generalize the variation in manual scoring of polysomnography and provide reference data for automatic sleep stage scoring systems. The reliability of manual scorers of polysomnography sleep stages was substantial. However, for certain stages, the results were poor; validity requires improvement. CITATION: Lee YJ, Lee JY, Cho JH, Choi JH. Interrater reliability of sleep stage scoring: a meta-analysis. J Clin Sleep Med. 2022;18(1):193-202.

Uvulopalatopharyngoplasty may decrease the incidence of Parkinson's disease associated with obstructive sleep apnea.

The purpose of this study was to investigate whether the incidence of Parkinson's disease (PD) is increased among patients with obstructive sleep apnea (OSA) and whether surgical treatment can prevent such an increase. This was a retrospective cohort study. We analysed the claims data from the Korea National Health Insurance Service. A total of 202,726 patients who were newly diagnosed with OSA between 2007 and 2014 were included. The patients were divided into two groups: patients who underwent uvulopalatopharyngoplasty (surgery group, n = 22,742) and those who did not (conservative group, n = 179,984). The control group (n = 1,013,630) was selected by propensity score matching. They were tracked until 31st December 2015. The hazard ratio of PD diagnosis (95% confidence interval) in the OSA group with respect to the control group was calculated using the Cox proportional hazard model. In the conservative group, the incidence of PD (hazard ratio 2.57 [2.32-2.85]) was significantly higher than that in the control group, while the incidence of PD in the surgery group was similar to that in the control group (hazard ratio 1.45 [0.89-2.22]). Patients with OSA are at an increased risk of developing PD, and uvulopalatopharyngoplasty may mitigate this risk.

Association between obstructive sleep apnea and thyroid cancer incidence: a national health insurance data study.

PURPOSE: Little is known about the incidence of thyroid cancer in patients with obstructive sleep apnea (OSA). This study aimed to evaluate whether OSA is associated with the incidence of thyroid cancer based on the Korea National Health Insurance Service (KNHIS) database. METHODS: This study was designed as a retrospective cohort data analysis of the KNHIS dataset. A total of 198,574 patients who were over 20 years of age and had been newly diagnosed with OSA between 2007 and 2014 were enrolled. A control group of 992,870 individuals was selected based on propensity score matching by age and sex. The mean follow-up duration was 4.5 ± 2.3 years. The primary endpoint was the incidence of newly diagnosed thyroid cancer. RESULTS: The hazard ratio (HR) for thyroid cancer incidence among OSA patients compared to the control was 1.72 (95% confidence interval [CI] 1.60-1.84) based on Model 1 (not adjusted by any covariate) and 1.64 (95% CI 1.53-1.76) based on Model 2 (adjusted by income level, diabetes, hypertension, and dyslipidemia). Thyroid cancer incidence was significantly higher in male patients (HR = 1.93, 95% CI 1.74-2.12) than female ones (HR = 1.39, 95% CI 1.26-1.54). When compared by age, the HR of thyroid cancer was higher in middle-aged (40 ≤ age < 65 years) patients (HR = 1.68, 95% CI 1.55-1.83) than in young (20 ≤ age < 40 years, HR = 1.53, 95% CI 1.32-1.77) or old (65 ≤ age, HR = 1.28, 95% CI 0.94-1.74) patients. CONCLUSION: OSA may increase the risk of developing thyroid cancer, especially in middle-aged men.

High Mobility Group Box Chromosomal Protein-1 Induces Myofibroblast Differentiation and Extracellular Matrix Production via RAGE, p38, JNK and AP-1 Signaling Pathways in Nasal Fibroblasts.

BACKGROUND: Chronic rhinosinusitis is involved in myofibroblast differentiation and extracellular matrix (ECM) accumulation. High mobility group box chromosomal protein 1 (HMGB-1) is known to stimulate lung fibroblast to produce ECM in lung fibrosis. The aim of this study was to investigate whether HMGB-1 induces myofibroblast differentiation and ECM production in nasal fibroblasts and to identify the signal pathway. METHODS: Human nasal fibroblasts were cultured. After stimulation with HMGB-1, expressions of α-smooth muscle actin (α-SMA) and fibronectin were determined by real-time PCR and western blot. Total collagen was measured by Sircol assay. To investigate signal pathway, various signal inhibitors and RAGE siRNA were used. RESULTS: HMGB-1 increased α-SMA and fibronectin in mRNA and protein levels. It also increased collagen production. RAGE siRNA inhibited HMGB-1-induced α-SMA and fibronectin, and production of collagen. Furthermore, the inhibitors of RAGE downstream molecules such as p38, JNK and AP-1 also blocked the HMGB-1-induced effects. CONCLUSIONS: HMGB-1 induces myofibroblast differentiation and ECM production in nasal fibroblast, which is mediated by RAGE, p38, JNK and AP-1 signal pathway. These results suggest that HMGB-1 may play an important role in tissue remodeling during chronic rhinosinusitis progression.