Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, P. R. of China.
BMC Nephrol. 2020 Jul 14;21(1):274. doi: 10.1186/s12882-020-01931-5.
Mitochondrial dysfunction contributes to the pathogenesis of diabetic nephropathy (DN). Mitochondrial pyruvate carrier 1 (MPC1) and mitochondrial pyruvate carrier 2 (MPC2) play a bottleneck role in the transport of pyruvate into mitochondrial across the mitochondrial inner membrane. A previous study showed that increasing mitochondrial pyruvate carrier content might ameliorate diabetic kidney disease in db/db mice. However, the expression status of MPC1 and MPC2 in patients with DN is unclear.
Patients with primary glomerulonephropathy (PGN, n = 30), PGN with diabetes mellitus (PGN-DM, n = 30) and diabetic nephropathy (DN, n = 30) were included. MPC1 and MPC2 protein levels were examined by immunohistochemistry. The expression of MPC in different groups was evaluated by the Kruskal-Wallis test. Spearman's rank correlation was performed for correlation analysis between MPC levels and clinical factors.
Both MPC1 and MPC2 were localized in renal tubules. Levels of MPC1 and MPC2 were lower in DN patients than in PGN patients and in PGN patients with DM, whereas there were no differences in MPC1 and MPC2 levels among DN stage II to stage IV. Moreover, both MPC1 and MPC2 levels were significantly correlated with serum creatinine, BUN and eGFR in patients with DN, whereas no analogous trend was observed in nondiabetic kidney disease.
Our study indicated that MPC localized in renal tubules, which were significantly decreased in DN. MPC was associated with clinical features, especially those representing renal functions.
线粒体功能障碍导致糖尿病肾病（DN）的发病机制。线粒体丙酮酸载体 1（MPC1）和线粒体丙酮酸载体 2（MPC2）在丙酮酸穿过线粒体内膜进入线粒体的运输中起着瓶颈作用。先前的研究表明，增加线粒体丙酮酸载体的含量可能改善 db/db 小鼠的糖尿病肾病。然而，DN 患者 MPC1 和 MPC2 的表达状态尚不清楚。
纳入原发性肾小球肾炎（PGN，n=30）、合并糖尿病的 PGN（PGN-DM，n=30）和糖尿病肾病（DN，n=30）患者。通过免疫组织化学法检测 MPC1 和 MPC2 蛋白水平。采用 Kruskal-Wallis 检验评估不同组中 MPC 的表达。采用 Spearman 秩相关分析 MPC 水平与临床因素之间的相关性。
MPC1 和 MPC2 均定位于肾小管。DN 患者的 MPC1 和 MPC2 水平低于 PGN 患者和 PGN-DM 患者，而在 DN Ⅱ期至Ⅳ期患者中，MPC1 和 MPC2 水平无差异。此外，MPC1 和 MPC2 水平与 DN 患者的血清肌酐、BUN 和 eGFR 均呈显著相关，而在非糖尿病肾病患者中则无类似趋势。
本研究表明，定位于肾小管的 MPC 在 DN 中明显减少。MPC 与临床特征相关，特别是与肾功能相关。
