Abstract
The aim of this study was to investigate whether Tripterygium wilfordii Hook F (TwHF) and irbesartan could synergistically affect the urinary excretion of podocytes and proteins in type 2 diabetic kidney disease (DKD) patients and the underlying mechanisms. Forty DKD patients were divided into a DI group (DKD patients treated with irbesartan alone) and a DTI group (DKD patients treated with Tripterygium wilfordii Hook F and irbesartan). Urinary podocytes were observed by immunofluorescence. Urinary levels of connective tissue growth factor (CTGF) and transforming growth factor-β1 (TGF-β1) were detected by enzyme-linked immunosorbent assay. Immunofluorescence indicated that shed podocytes were not detected in urine samples of normal controls, whereas the detection rate of urinary podocytes was 82.5% in DKD patients. Urinary CTGF and TGF-β1 levels were significantly higher in urinary podocyte-positive DKD patients than in urinary podocyte-negative patients. Furthermore, urinary podocyte excretion was closely correlated with urinary protein excretion and urinary CTGF/TGF-β1 levels. Treatments with TwHF and irbesartan significantly reduced the urinary excretion of proteins and podocytes, and decreased the urinary levels of CTGF and TGF-β1. Our results suggest that urinary podocyte excretion might serve as a predictor for DKD progression. TwHF/irbesartan combination could reduce the urinary excretion of proteins and podocytes synergistically in DKD patients, which might result from the synergistic inhibition of CTGF and TGF-β1 in urine.
Highlights
Glomerular podocytes, a special type of epithelial cells, play an important role in maintaining the integrity of the filtration barrier in kidneys
The staining indicated that shed podocytes were not detected in the urine of normal controls (Figure 1(A)), whereas they were found in urine samples from diabetic kidney disease (DKD) patients, with a detection rate of 82.5% (Figure 1(B)) (P < 0.01)
Our previous study has shown that triptolide could significantly reduce urinary protein excretion, improve podocyte ultrastructure, decrease renal podocyte proteins of nephrin and podocin and reduce the levels of pro-inflammatory factors of connective tissue growth factor (CTGF) and transforming growth factor-b1 (TGF-b1) in DKD model rats
Summary
Glomerular podocytes, a special type of epithelial cells, play an important role in maintaining the integrity of the filtration barrier in kidneys. Podocyte impairment has been shown to be involved in the development of proteinuria and the early pathological processes of diabetic kidney disease (DKD).[1,2] Recent studies indicate that the abnormal expression and distribution of podocyte surface marker proteins (such as nephrin and podocin), the reduction of podocytes, the loss of foot process fusion and other pathological changes may induce DKD and promote the disease progression.[3,4]. It is of great importance to investigate the impairment of podocytes in kidney disease. Recent studies have found that podocytes shed in urine could serve as an indicator for disease progression in primary or secondary glomerular lesions, including DKD.[5,6]
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