Department of Pathology, Genetics and Evolution, Discipline of General Pathology, Institute of Biological and Natural Sciences of Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil.
Institute of Nephropathology, Center for Electron Microscopy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
PLoS One. 2023 May 2;18(5):e0284789. doi: 10.1371/journal.pone.0284789. eCollection 2023.
Diabetic nephropathy (DN) is the leading cause of chronic kidney disease and end-stage renal failure worldwide. Several mechanisms are involved in the pathogenesis of this disease, which culminate in morphological changes such as podocyte injury. Despite the complex diagnosis and pathogenesis, limited attempts have been made to establish new biomarkers for DN. The higher concentration of Mindin protein in the urine of patients with type 2 diabetes mellitus suggests that it plays a role in DN. Therefore, this study investigated whether in situ protein expression of Mindin can be considered a potential DN biomarker. Fifty renal biopsies from patients diagnosed with DN, 57 with nondiabetic glomerular diseases, including 17 with focal segmental glomerulosclerosis (FSGS), 14 with minimal lesion disease (MLD) and 27 with immunoglobulin A nephropathy (IgAN), and 23 adult kidney samples from autopsies (control group) were evaluated for Mindin expression by immunohistochemistry. Podocyte density was inferred by Wilms' tumor 1 (WT1) immunostaining, while foot process effacement was assessed by transmission electron microscopy. Receiver operative characteristic (ROC) analysis was performed to determine the biomarker sensitivity/specificity. Low podocyte density and increased Mindin expression were observed in all cases of DN, regardless of their class. In the DN group, Mindin expression was significantly higher than that in the FSGS, MCD, IgAN and control groups. Higher Mindin expression was significantly positively correlated with foot process effacement only in class III DN cases. Furthermore, Mindin protein presented high specificity in the biopsies of patients with DN (p < 0.0001). Our data suggest that Mindin may play a role in DN pathogenesis and is a promising biomarker of podocyte lesions.
糖尿病肾病（DN）是全球慢性肾脏病和终末期肾衰竭的主要原因。该疾病的发病机制涉及多种机制，最终导致足细胞损伤等形态学变化。尽管诊断和发病机制复杂，但很少有尝试建立新的 DN 生物标志物。Mindin 蛋白在 2 型糖尿病患者尿液中的浓度较高，提示其在 DN 中发挥作用。因此，本研究探讨了 Mindin 的原位蛋白表达是否可被视为潜在的 DN 生物标志物。通过免疫组织化学法评估了 50 例经诊断患有 DN 的患者、57 例非糖尿病肾小球疾病患者（包括 17 例局灶节段性肾小球硬化症[FSGS]患者、14 例微小病变性疾病[MLD]患者和 27 例免疫球蛋白 A 肾病[IgAN]患者）和 23 例成人尸检肾脏样本（对照组）的 Mindin 表达情况。通过 Wilms 肿瘤 1（WT1）免疫染色推断足细胞密度，而通过透射电子显微镜评估足突融合。进行受试者工作特征（ROC）分析以确定生物标志物的敏感性/特异性。无论 DN 属于何种类型，所有病例均观察到低足细胞密度和 Mindin 表达增加。在 DN 组中，Mindin 表达明显高于 FSGS、MCD、IgAN 和对照组。仅在 III 期 DN 病例中，Mindin 表达的升高与足突融合显著呈正相关。此外，Mindin 蛋白在 DN 患者的活检标本中具有高特异性（p<0.0001）。我们的数据表明，Mindin 可能在 DN 的发病机制中发挥作用，是足细胞损伤的有前途的生物标志物。
