ABSTRACT
In recent years, with the development of metabolic reprogramming research, people have changed their understanding of the biological effects of immune cells. Under the stimulation of inflammatory response, immune cells re-regulate their metabolism and bioenergetics, provide energy and substrates for cell survival, and initiate immune effect functions. Nod-like receptor protein 3 (NLRP3) inflammasome, as an important component of the innate immune system, has been shown to sense metabolites such as uric acid and cholesterol crystals, and can be inhibited by metabolites such as ketones. It is also regulated by mitochondrial reactive oxygen species and glycolytic components (such as hexokinase). Recent studies have shown that a variety of metabolic pathways converge as effective regulators of NLRP3 inflammasome. The paper reviews the metabolic regulatory pathways and specificity of NLRP3 inflammasome activation, and its role in renal diseases.
ABSTRACT
Objective To detect the serum microRNA-148b-3p level in patients with diabetes mellitus and diabetic nephropathy,and to analyze its correlation with clinical and pathological indexes.Methods The research crowd was divided into three groups (1) diabetic nephropathy group:biopsy with diabetic nephropathy (n=25,14 males,11 females);(2) type 2 diabetes mellitus group:type 2 diabetes mellitus patients with normal urinary microalbumin/urinary creatinine value (n=10,4 males,6 females);(3) normal control group:healthy subjects (n=9,3 males and 6 females).Clinical indicators included gender,age,24-hour urine protein,systolic blood pressure (SBP),diastolic blood pressure (DBP),serum creatinine (Scr),urea (Urea),cystatin-C (Cys-C),blood albumin (ALB),urine microalbumin (UMA),triacylglycerol (TG),total cholesterol (TC),high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C),serum uric acid (UA),fasting blood glucose (FBG),glycated hemoglobin (HbA1c),urine microalbuminuria / urinary creatinine (UACR),and estimated glomerular filtration rate (eGFR) calculated by CKD-EPI formula.Real-time quantitative PCR was applied to verify the expression of microRNA-148b-3p in serum samples of the research crowds.The relationships between microRNA-148b-3p level and clinical features was also analyzed.Results The levels of serum microRNA-148b-3p in diabetic nephropathy group and in type 2 diabetes mellitus group were 1.82 times and 1.73 times of that in normal control group (P ＜ 0.05,respectively).The level of serum microRNA-148b-3p was significantly correlated with HDL-C (r=-0.374,P=0.013),UMA (r=0.426,P=0.004),FBG (r=0.330,P=0.046) and TG (r=0.423,P=0.005).Multiple linear regression analysis showed that UMA level was independently associated with serum microRNA-148b-3p level (β=0.338,P=0.044).The area under the receiver operating characteristic curve (ROC) of serum microRNA-148b-3p in diagnosing type 2 diabetes mellitus and diabetic nephropathy was 0.835 and 0.665,respectively.Conclusions The level of serum microRNA-148b-3p of patients with type 2 diabetes mellitus or diabetic nephropathy significantly increases.The level of UMA is independently associated with serum microRNA-148b-3p level.Serum microRNA-148b-3p is expected to be a potential biomarker for the diagnosis of diabetic nephropathy.