Tumour necrosis factor-related apoptosis-inducing ligand expression in patients with diabetic nephropathy

Abstract

Objective:The objective of this study was to evaluate the expression profile of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in patients with diabetic nephropathy (DN).Methods:A total of 126 Chinese subjects were enrolled in this study, including 42 patients with diabetes mellitus (DM), 42 patients with DN and 42 healthy controls. Real-time polymerase chain reaction was performed to analyze levels of TRAIL mRNA in peripheral blood mononuclear cells (PBMCs). Serum levels of soluble TRAIL (sTRAIL) and various cytokines were detected with a commercially available enzyme-linked immunosorbent assay kit.Results:Compared with the control group, the levels of TRAIL mRNA in PBMCs and sTRAIL in sera were both significantly decreased in the DM and DN patients (P < 0.05). Conversely, levels of interleukin (IL)-1, IL-6, tumour necrosis factor-α and monocyte chemotactic protein-1 were higher in the DN group than in the control group. Serum levels of TRAIL positively correlated with TRAIL mRNA levels in all of the subjects examined (P < 0.05).Conclusions:These results provide support and a theoretical basis for further research of TRAIL in regard to the pathogenesis of DN.

<p>Curcumin Inhibited Podocyte Cell Apoptosis and Accelerated Cell Autophagy in Diabetic Nephropathy via Regulating Beclin1/UVRAG/Bcl2</p>

“…Previous studies have shown that the interaction between apoptosis and DN included complex pathways and molecular and confirmed the important role of apoptosis pathways in DN. [41][42][43] The B-cell lymphoma 2 family proteins are central regulators of intracellular apoptotic signaling cascades. In this study, WB showed that increased anti-apoptotic protein Bcl-2, and decreased pro-apoptotic protein Bax and caspase-3 in the curcumin group than the DN group in vivo.…”

Repositioning the Role of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) on the TRAIL to the Development of Diabetes Mellitus: An Update of Experimental and Clinical Evidence

“…Table 2 summarizes the major experimental and clinical studies investigating the relationship of TRAIL with T2DM in animals and humans [ 16 , 17 , 19 , 20 , 24 , 27 , 28 , 30 , 33 , 57 ].…”

“…In humans, reduced circulating TRAIL levels have been reported in several cohorts of T2DM patients with diabetic nephropathy compared with healthy individuals [ 27 , 28 , 57 ]. In 112 patients with T2DM, the presence of microalbuminuria was associated with lower serum TRAIL levels compared to non-diabetic controls [ 57 ].…”

“…There has been an increased interest in exploiting the potential of TRAIL to treat metabolic diseases [ 12 , 13 ], based on a growing body of experimental and clinical evidence suggesting that the TRAIL system plays an important role in the development and progression of both autoimmune (T1DM) and obesity-associated (T2DM) diabetes mellitus [ 13 , 14 ]. The association of TRAIL with diabetes becomes evident through a number of findings provided by animal and human studies, which briefly comprise the following: (i) the onset and severity of T1DM and T2DM can be accelerated and exacerbated by TRAIL blockade or TRAIL genetic deficiency [ 15 , 16 , 17 ], (ii) T1DM and T2DM can be effectively prevented and ameliorated by recombinant TRAIL treatment or systemic TRAIL gene delivery [ 18 , 19 , 20 , 21 , 22 ], (iii) circulating soluble TRAIL levels are significantly reduced in patients with T1DM, T2DM and diabetes-related macro- and microvascular complications [ 23 , 24 , 25 , 26 , 27 , 28 , 29 ], (iv) serum TRAIL levels of patients with T2DM progressively increase upon antidiabetic treatment [ 30 ]. To explore the underlying mechanisms accounting for the TRAIL-diabetes relationship, several in vitro studies have been conducted and report direct effects of TRAIL on several tissues involved in diabetes pathophysiology, such as pancreatic islets, skeletal muscle, adipose tissue, liver, kidney, and immune and vascular cells [ 7 , 20 , 31 , 32 , 33 , 34 ].…”

TRAIL, OPG, and TWEAK in kidney disease: biomarkers or therapeutic targets?

“…Clinical studies have shown that TRAIL levels are significantly lower in patients with T1DM [17] and T2DM [188,189] at onset as compared with healthy subjects, and that this reduction becomes less pronounced a few months after the start of the therapy [17,188]. A decrease in circulating TRAIL has been found also in patients with diabetic nephropathy as compared with healthy controls [190][191][192]. By contrast, studies on the tissue expression of TRAIL have shown that in T1DM patients there is an increase in TRAIL positive T-cells [193,194].…”