Department of Thyroid Surgery, General surgery center, The First Hospital of Jilin University, Changchun, China.
Department of Nephrology, The First Hospital of Jilin University, Changchun, China.
FASEB J. 2023 Oct;37(10):e23188. doi: 10.1096/fj.202300708R.
Diabetic nephropathy (DN) is an important complication of diabetes and the leading cause of end-stage renal disease globally. Renal tubular damage occurs to varying degrees in the early stages of DN prior to glomerular damage. Renalase (RNLS) is an amine oxidase, which is produced and secreted by the renal tubular epithelial cells. RNLS is reportedly closely related to renal tubular injury in acute and chronic kidney diseases. Herein, we aimed to evaluate the changes in tubular RNLS expression in DN and its correlation with DN-associated renal tubular injury. Conditional permanent renal tubular epithelial rat-cell line NRK-52E was transfected with pcDNA3-RNLS plasmid or administered recombinant rat RNLS protein and high glucose (HG) dose. A total of 22 adult Sprague-Dawley rats were randomly divided into the control (CON, n = 10) or diabetic nephrology (DN, n = 12) group. Random blood glucose levels of the rats were measured by sampling of the caudal vein weekly. After 8 weeks, the rat's body weight, 24-h urinary albumin concentration, and right kidney were evaluated. Our study suggested the decreased expression levels of RNLS in renal tissue and renal tubular epithelial cells in DN rats, accompanied by renal tubulointerstitial fibrosis, apoptosis of renal tubular epithelial cells, and activation of the p38MAPK signal pathway. Reversing the low RNLS expression can reduce the level of p38MAPK phosphorylation and delay renal tubular injury. Thus, the reduction of renal tubular RNLS expression in DN mediates tubulointerstitial fibrosis and cell apoptosis via the activation of the p38MAPK signal pathway. RNLS plays a key mediating role in DN-associated tubular injury via p38MAPK, which provides new therapeutic targets and a theoretical basis for early prevention and treatment of DN.
糖尿病肾病（DN）是糖尿病的一种重要并发症，也是全球范围内导致终末期肾病的主要原因。在肾小球损伤之前，DN 的早期阶段会发生不同程度的肾小管损伤。肾钠肽酶（RNLS）是一种胺氧化酶，由肾小管上皮细胞产生和分泌。据报道，RNLS 与急性和慢性肾脏病的肾小管损伤密切相关。在此，我们旨在评估 DN 中肾小管 RNLS 表达的变化及其与 DN 相关的肾小管损伤的相关性。用 pcDNA3-RNLS 质粒转染条件性永生化大鼠肾小管上皮细胞系 NRK-52E 或给予重组大鼠 RNLS 蛋白和高糖（HG）剂量。总共 22 只成年 Sprague-Dawley 大鼠被随机分为对照组（CON，n=10）或糖尿病肾病组（DN，n=12）。每周通过尾静脉取血测量大鼠的随机血糖水平。8 周后，评估大鼠的体重、24 小时尿白蛋白浓度和右肾。我们的研究表明，DN 大鼠肾组织和肾小管上皮细胞中 RNLS 的表达水平降低，同时伴有肾间质纤维化、肾小管上皮细胞凋亡和 p38MAPK 信号通路的激活。逆转低 RNLS 表达可降低 p38MAPK 磷酸化水平并延缓肾小管损伤。因此，DN 中肾小管 RNLS 表达的降低通过激活 p38MAPK 介导小管间质纤维化和细胞凋亡。RNLS 通过 p38MAPK 在 DN 相关的管状损伤中发挥关键的介导作用，为早期预防和治疗 DN 提供了新的治疗靶点和理论依据。
