Published online Jan 15, 2021. doi: 10.4239/wjd.v12.i1.19
Peer-review started: August 21, 2020
First decision: September 21, 2020
Revised: October 5, 2020
Accepted: October 26, 2020
Article in press: October 26, 2020
Published online: January 15, 2021
With the increasing incidence of diabetes, the incidence of diabetic kidney disease (DKD) continues to rise, which has become the leading cause of end-stage renal disease. However, current treatments like angiotensin-converting enzyme inhibitors only partially inhibited the DKD progression. Thus, the mechanisms underlying DKD should be clarified and disclosed, and new strategies for delaying the progression are urgently needed.
By testing the serum tenascin-C (TNC) level in patients with type 2 diabetic mellitus (T2DM), we aim to provide insights into the pathogenesis of the DKD and suggest that TNC can serve as a therapeutic target for this disease.
In the present study, we evaluated the alterations of TNC expression levels in the serum or/and glomeruli of patients with T2DM and rats with streptozotocin-induced diabetes. We also evaluated the diagnose indexes of DKD, including glycosylated hemoglobin (HbA1c) level, body mass index (BMI), systolic blood pressure (SBP), and urinary albumin to creatinine ratio (UACR) in the serum of patients. In addition, we explored the specific molecular mechanism of TNC on DKD by culturing rat glomerular mesangial cells.
Diabetes patient serum samples were collected to detect the expression level of TNC in serum and make analysis with other related factors in diabetes. Diabetic rat models were used to observe the expression of TNC in diabetic rat kidney, and enzyme-linked immunosorbent assay was used to detect the expression of TNC in diabetic rat serum, and analyze the associated renal function indexes. SiRNA transfection technique was used in cultured rat glomerular mesangial cells stimulated with high glucose to explore the molecular mechanisms of TNC in DKD.
Diabetic patients had significantly increased serum levels of TNC, and TNC was positively correlated with UACR, BMI, SBP, and DBP. TNC expression in diabetic rat kidney increased obviously, and diabetic rats had significantly higher serum TNC expression levels compared with normal rats. Urea nitrogen and creatinine were positively correlated with the increase of TNC in diabetic rats. Rat glomerular mesangial cells stimulated with high glucose had significantly increased protein expression of TNC, and TNC can promote inflammation and fibrosis through the Toll-like receptor 4/nuclear factor-κB pathway. Metformin can inhibit the expression of TNC and delay the progress of DKD.
We demonstrated that increased TNC expression is involved in the cascade of DKD. Importantly, inhibition of TNC delays the development of DKD, indicating that TNC represents a potential therapeutic target in DKD.
By targeting TNC expression, the occurrence and development of DKD can be delayed.