Abstract
BackgroundMitochondrial 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.MethodsPatients 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.ResultsBoth 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.ConclusionsOur 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.
Highlights
Mitochondrial dysfunction contributes to the pathogenesis of diabetic nephropathy (DN)
Measurements The following clinical data of patients were collected at the time of renal biopsy: age, gender, duration of diabetes, blood pressure, fasting glucose, glycosylated hemoglobin (HbA1C), blood urea nitrogen (BUN), serum creatinine, neutrophil gelatinase-associated lipocalin (NGAL), urine albumin, urine albumin-to-creatinine ratio (ACR) and so on
Patients characteristics A total of 90 patients were included in this study and categorized into three groups according to the renal biopsy: those with biopsy-proven diabetic nephropathy (DN group, n = 30), those with biopsy-proven primary glomerulonephropathy (PGN group, n = 30), and those with biopsy-proven PGN and with diabetes mellitus (PGN-DM group, n = 30)
Summary
Mitochondrial dysfunction contributes to the pathogenesis of diabetic nephropathy (DN). A previous study showed that increasing mitochondrial pyruvate carrier content might ameliorate diabetic kidney disease in db/db mice. Hyperglycemia increased the tricarboxylic acid cycle and altered the glycolytic pathway via the elevated level of advanced glycation end products, the activity of protein kinase C and hexosamine pathways and so on, which contributed to mitochondrial dysfunction [8, 11]. There were some investigations of patients and animal models have confirmed that mitochondrial dysfunction was postulated as a primary initiator and played a pivotal role in the progression of DN [12,13,14,15]. Therapies that target mitochondrial function would be beneficial to alleviate DN progression, which has been verified by several mitochondria-targeted antioxidants including coenzyme Q10, mitoquinone, MTP-131 and so on [16,17,18]
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