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
1992年中山医科大学本科毕业，1999年获医学硕士学位，从事整形美容、癫痕治疗、创面修复临床工作近二十年。
教授，医学博士，博士研究生导师，硕士研究生导师。毕业于第三军医大学军医系，现任广州军区总医院整形外科主任兼全军激光整形中心主任。从事整形美容外科工作20余年，临床经验丰富，专科技术全面。
擅长：四肢血管损伤/周围神经损伤的外科治疗。带血管蒂组织瓣转位修复骨外露/钢板外露/组织缺损。先天性唇腭裂/先天性手畸形的整复。乳房缺陷的整形。手外伤I期/II期整复。血管瘤的外科治疗。
从事整形美容工作近30年，具有扎实的整形美容外科基础，擅长各种疤痕及溃疡创面的处理，血管瘤等浅表肿瘤的治疗；
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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