ABSTRACT
Diabetic nephropathy (DN) is one of the most common causes for end-stage renal disease without effective therapies available. NLR family, pyrin domain-containing 3 (NLRP3) inflammasome possesses a fundamental effect to facilitate the pathogenesis of DN. Unfortunately, how NLRP3 inflammasome is mediated still remains largely unclear. In the present study, an E3 ubiquitin ligase Speckle-type BTB-POZ protein (Spop) was identified as a suppressor of NLRP3 inflammasome. We first showed that Spop expression was extensively down-regulated in kidney of DN patients, which was confirmed in kidney of streptozotocin (STZ)-challenged mice and in high glucose (HG)-stimulated podocytes. Intriguingly, we showed that conditional knockout (cKO) of Spop in podocytes considerably accelerated renal dysfunction and pathological changes in the glomerulus of STZ-induced mice with DN, along with severe podocyte injury. Furthermore, Spop specific ablation in podocytes dramatically facilitated inflammatory response in glomeruli of DN mice via enhancing NLRP3 inflammasome and nuclear factor κB (NF-κB) signaling pathways, which were confirmed in HG-cultured podocytes. Notably, our findings indicated that Spop directly interacted with NLRP3. More importantly, Spop promoted NLRP3 degradation via elevating K48-linked polyubiquitination of NLRP3. Collectively, our findings disclosed a mechanisms through which Spop limited NLRP3 inflammasome under HG condition, and illustrated that Spop may be a novel therapeutic target to suppress NLRP3 inflammasome, contributing to the DN management.
Subject(s)
Diabetic Nephropathies/metabolism , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Nuclear Proteins/physiology , Repressor Proteins/physiology , Ubiquitin-Protein Ligase Complexes/physiology , Animals , Blood Glucose/metabolism , Down-Regulation , HEK293 Cells , Humans , Inflammation , Kidney/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Microscopy, Electron, Transmission , Nuclear Proteins/metabolism , Podocytes/metabolism , Signal Transduction , Streptozocin , Ubiquitin/chemistry , Ubiquitin-Protein Ligases/chemistryABSTRACT
ABSTRACT: This study aimed to evaluate the prevalence of low health literacy in Hebei Province of China, and to investigate its socio-demographic risk factors.This study was a community-based, cross-sectional questionnaire survey with a multiple-stage randomization design and a sample size of 10,560. Participants' health literacy status was evaluated by a questionnaire based on the 2012 Chinese Resident Health Literacy Scale. Meanwhile, participants' socio-demographic characteristics were also collected by the questionnaire.A total of 9952 participants provided valid questionnaires and were included in the final analyses. The mean health literacy score was 63.1â±â17.1 points; for its subscales, the mean basic knowledge and concepts score, lifestyle score, health-related skills score were 31.7â±â9.0, 17.2â±â4.8, 14.3â±â4.1, respectively. Meanwhile, low health literacy prevalence was 81.0%; for its subscales, low basic knowledge and concepts prevalence (70.6%) was numerically reduced compared to low lifestyle prevalence (87.4%) and low health-related skills prevalence (86.1%). Further analyses showed that age, male, and rural area were positively associated, but education level and annual household income were negatively associated with low health literacy prevalence. Further multivariate logistic regression analyses showed that higher age, male, lower education level, lower annual household income, and rural area were closely correlated with the risks of low total health literacy or low health literacy in subscales in Hebei Province.The prevalence of low health literacy is 81.0% in Hebei Province. Meanwhile, higher age, male, lower education level, lower annual household income, and rural area closely associate with low health literacy risk.
Subject(s)
Health Literacy/statistics & numerical data , Adolescent , Adult , Age Factors , Aged , China , Cross-Sectional Studies , Educational Status , Female , Humans , Income , Life Style , Male , Middle Aged , Risk Factors , Rural Population/statistics & numerical data , Sex Factors , Urban Population/statistics & numerical data , Young AdultABSTRACT
ABSTRACT: This study aimed to evaluate the low health literacy prevalence and its socio-demographic related factors in Xingtai.This study was a community-based, cross-sectional survey performed in Xingtai, with a sample size of 960. Participants' socio-demographic characteristics were collected, and their health literacy status was evaluated by the questionnaire designed by the 2012 Chinese Resident Health Literacy Survey.There were 904 (94.2%) participants who provided valid questionnaires and they were included in the analyses. The mean health literacy score was 63.0â±â16.6; for its subscales, the mean scores of health literacy of basic knowledge and concepts, lifestyle, and health-related skills were 31.6â±â8.7, 17.1â±â4.7, and 14.3â±â3.9, respectively. Low total health literacy prevalence was 83.1%; as for its subscales, the prevalence of low health literacy of basic knowledge and concepts, lifestyle, and health-related skills was 72.5%, 87.8%, and 87.4%, respectively. Meanwhile, age, male and rural location were positively correlated, but education level and annual household income were negatively correlated with low health literacy risk. Further multivariate analysis revealed that lower education level was the only independent related factor for low total health literacy, and the most important independent related factor for low total health literacy of basic knowledge and concepts, lifestyle and health-related skills.Low health literacy prevalence is 83.1%, and lower education level is the most critical related factor for low health literacy in Xingtai.
