Lin Liao1 · Qiming Xu2 · Jie Xu3 · Jie Chen1 · Wenrui Liu1 · Wenhao Chen1 · Yunqing Tang1 · Lianxiang Duan1 · Yue Guo1 · Ziyang Liu1 · Pengyu Tao2 · Yu Cao2 · Jianrao Lu1 · Jing Hu1,4
Received: 14 June 2024 / Accepted: 31 January 2025 / Published online: 13 February 2025 © The Author(s) 2025
Abstract
Aims One of the primary pathological features in the early stages of diabetic nephropathy is mesangial cell (MC) hypertro-phy in the glomerulus. Considering the role of E3 ubiquitin ligases in regulating MC hypertrophy, the aim of this study was to identify the functional ubiquitin protein ligase E3 component N-recognin 5 (UBR5) during MC hypertrophy under high glucose conditions.
Methods Human MCs (HMCs) transduced with UBR5 silencing or overexpression vector were treated with high glucose, AKT inhibitor, or glycolysis inhibitor. Cell proliferation, cell cycle, hypertrophy and glycolysis were evaluated in the HMCs after indicated treatment. m6A methylated RNA immunoprecipitation, luciferase reporter assay, and RNA immunoprecipi-tation were performed to determine the regulation of UBR5 by Wilms tumor 1-associating protein (WTAP)/insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) induced m6A modification. Western blot was performed to determine the protein expression levels.
Results UBR5 expression was upregulated in db/db mice and in high glucose-induced HMCs. UBR5 silencing inhibited high glucose-induced HMC cell cycle arrest, cell hypertrophy, and glycolysis. UBR5 facilitated HMC hypertrophy and gly colysis by promoting the phosphorylation levels of AKT. Additionally, the promoting effect of glycolysis on cell hypertrophy were also elucidated. Further investigation into upstream regulators revealed that WTAP promoted m6A modification of UBR5 through the m6A reader IGF2BP1.
Conclusions Our study unveils a novel mechanism involved in high glucose-induced cell hypertrophy, offering new insights into the understanding and treatment of early pathological mechanisms in diabetic nephropathy.
Keywords High glucose · Hypertrophy · Glycolysis · UBR5, AKT phosphorylation
Maria Ida Maiorino1,2 · Carlo Gesualdo3,4 · Silvia Angelino5 · Settimio Rossi3 · Nicole Di Martino2 · Clemente Iodice3,5 · Miriam Longo1,4 · Lorenzo Scappaticcio1,2 · Giuseppe Bellastella1,2 · Francesca Simonelli3 · Katherine Esposito1,2,5
Received: 4 January 2026 / Accepted: 6 May 2026 © The Author(s) 2026
Aims To investigate the independent association between long-term glycemic variability, measured as the coefficient of variation (CV) of HbA1c, and the presence of diabetic retinopathy (DR) in a cohort of adults with diabetes within a system-atic eye screening program.
Methods This study screened 379 adults with type 1 and type 2 diabetes. Long-term glycemic variability was calculated as the CV of serial HbA1c measurements. DR was assessed via dilated fundus photography. The association between HbA1c CV and DR was analyzed using multivariable logistic regression adjusting for confounders.
Results DR incidence of 12.4%, mostly mild non-proliferative. The median HbA1c CV was 7.0% (53 mmol/mol). In unad-justed bivariate analysis, the incidence of mild DR was higher in the low- glycemic variability group (CV<5%) compared to the high- glycemic variability group. However, the multivariable logistic regression analysis revealed that higher HbA1c CV was independently associated with the presence of DR (β=0.643, P=0.042), alongside diabetes duration (P<0.001) and age (P<0.001).
Conclusions In conclusion, in a cohort of individuals with both type 1 and type 2 diabetes and a low incidence of DR, long-term glycemic variability, estimated as HbA1c CV, was independently associated with an increased risk of this complication.
Keywords Diabetic retinopathy · Glucose variability · Type 1 diabetes · Type 2 diabetes · Retinopathy screening · HbA1c coefficient of variation
擅长:1. 烧伤/烫伤/手术疤痕美学修复; 2. 创面/伤口/溃疡/皮肤缺损美学修复; 3. 全身体表肿瘤/包块手术治疗。
擅长疾病:1.面部轮廓整形;2.面部年轻化;3.身体塑形;4.先天性和创伤后畸形修复、体表肿瘤切除及器官再造。如:黄褐斑、瘢痕疙瘩、减肥 。教授,整形外科副主任,医学博士后,毕业于西安第四军医大学临床医学系,毕业后留校。
在成人大面积烧伤的休克复苏、感染防治、多器官功能障碍综合征的防治、严重电烧伤和吸入性损伤的救治以及小儿重度和特重度烧伤的救治等方面有较高造诣。获黑龙江省科技进步三等奖2项,哈尔滨市科技进步二等奖1项,三等奖2项。
担任欧洲糖尿病学会会员、美国糖尿病学会会员、欧洲糖尿病学会糖尿病足研究组发起会员、中华医学会糖尿病学分会第2届足病学组组长、中国人民解放军内分泌学会副主任委员、北京内分泌学会副主任委员、北京糖尿病防治协会副理事长、北京市朝阳区预防医学会副会长、国家卫生部全国慢性病综合防治示范点专家组成员、中国疾病控制中心慢病中心糖尿病专家、第四军医大学兼职教授,悉尼大学客座教授,第四军医大学硕士研究生导师,中南大学湘雅三医院硕士研究生导师主任医师。
伤口世界平台生态圈,以“关爱人间所有伤口患者”为愿景,连接、整合和拓展线上和线下的管理慢性伤口的资源,倡导远程、就近和居家管理慢性伤口,解决伤口专家的碎片化时间的价值创造、诊疗经验的裂变复制、和患者的就近、居家和低成本管理慢性伤口的问题。
2019广东省医疗行业协会伤口管理分会年会
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