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
擅长疾病:在烧伤、创伤后瘢痕整形、先天性畸形、面部及躯干美容等方面临床经验丰富,具有较强的解决本专业疑难病例的能力及显微外科手术能力。
擅长领域:(1)耳廓、乳房、阴茎、鼻部等体表器官再造(2)体表软组织肿瘤切除与美容修复(3)脂肪移植与面部年轻化(4)血管瘤、鲜红斑痣等激光美容
对烧伤外科、整形外科及美容外科有较深的造谐,擅长大面积严重烧伤的救治,唇腭裂修复、软组织缺损的修复及各类美容整形和再造整形手术,每年完成大小各类手术360余例。
从事整形外科近30年,留美多年,熟练掌握面部美容、除皱、乳房整形、脂肪抽吸等各类美容整形外科手术及各种非手术美容(如肉毒毒素A注射除皱等),对外生殖器整形与再造,两性畸形和易性症的手术治疗等有较深入研究。
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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