Mitochondria-related reversal of early-stage diabetic nephropathy in donor kidney after transplantation in mice

Abstract

Background: Renal diabetic changes are frequent in kidney transplantation (KTx) donors. Whether these diabetic changes are reversible remains a topic of debate. This study aimed to test the hypothesized reversibility of diabetic changes after KTx.Methods: C57BL/6J mice were randomly divided into three groups: the control group, early-stage group (ESG), and advanced-stage group (ASG). Diabetes mellitus (DM) was induced in mice by intraperitoneal injection of streptozotocin (STZ) at 50 mg/kg body weight for five consecutive days. Blood glucose levels ≥16.7 mmol/L were indicative of diabetic mice. The kidneys from ESG and ASG were transplanted to control mice 12 or 32 weeks after STZ injection. Kidney tissue, blood, and 24-hour urine specimens of donor and recipient mice were collected before KTx and 28 days after KTx, respectively. We measured the body weight, blood glucose, histological changes, reactive oxygen species (ROS), apoptosis. Electron microscopy was also performed to evaluate the mitochondrial morphology. The expression of NADPH oxidases (NOXs) was assessed by qRT-PCR.Results: Kidneys from early-stage diabetic mice showed evidence of lesion reversal four weeks after KTx, including decreased urinary albumin and reversal of histological changes. Besides, mitochondrial swelling, oxidative stress, apoptosis, and overexpression of NOXs in the kidneys were also suppressed. Conversely, no changes were observed in kidneys from advanced-stage diabetic mice after KTx. Conclusions:We confirmed that early-stage but not advanced-stage diabetic nephropathy (DN) is reversible, which is related to reduced NOX expression and improvement in mitochondrial function. These results indicated that kidneys with early-stage DN could be used for KTx in clinical practice, as the disease may be reversed following KTx.

Tetrandrine mediates renal function and redox homeostasis in a streptozotocin-induced diabetic nephropathy rat model through Nrf2/HO-1 reactivation

“…These inflammatory mediators play pivotal roles in various cells, tissues, and organs. Following the effect of the inflammatory factors, the inflammatory mediator interleukin, interferon, TNF-α were released from the body (31). Tet has the role of calcium antagonism, which showed by inhibiting calmodulin activity and reducing neutrophil calcium.…”

Interleukin-1 receptor-associated kinase 2 promotes inflammatory reactions by activating the nuclear factor kappa-B signaling pathway in diabetic nephropathy

“…Diabetes was confirmed by blood glucose measurements using a glucometer (Roche, Switzerland) at post-injection day three. Mice with blood glucose levels ≥ 16.7 mmol/l were considered diabetic [ 16 ]. Model mice were then transfected with sh-IRAK2 or pcDNA3.1-NF-κB according to the grouping.…”