Metformin regulates inflammation and fibrosis in diabetic kidney disease through TNC/TLR4/NF-κB/miR-155-5p inflammatory loop

• 作者: Chuan Lv Jia-Yi Kang Jin-Yu Han Min Yang Qiu-Yue Wang Xiao-Yu Ma Yang Zhou Yi-Li Wang Ying Shao
• 来源期刊: 世界糖尿病杂志:英文版(电子版)
• 学科: 医学
• 关键词: TENASCIN-C miR-155-5p METFORMIN Type 2 diabetes mellitus Diabetic kidney disease Toll-like receptor 4
• 年，卷（期）: 2021,（1）
• 页码范围: 19-46
• 页数: 28页
• 分类号: R58

摘要

BACKGROUND Type 2 diabetes mellitus(T2DM)is significantly increasing worldwide,and the incidence of its complications is also on the rise.One of the main complications of T2DM is diabetic kidney disease(DKD).The glomerular filtration rate(GFR)and urinary albumin creatinine ratio(UACR)increase in the early stage.As the disease progresses,UACR continue to rise and GFR begins to decline until endstage renal disease appears.At the same time,DKD will also increase the incidence and mortality of cardiovascular and cerebrovascular diseases.At present,the pathogenesis of DKD is not very clear.Therefore,exploration of the pathogenesis of DKD to find a treatment approach,so as to delay the development of DKD,is essential to improve the prognosis of DKD.AIM To detect the expression of tenascin-C(TNC)in the serum of T2DM patients,observe the content of TNC in the glomerulus of DKD rats,and detect the expression of TNC on inflammatory and fibrotic factors in rat mesangial cells(RMCs)cultured under high glucose condition,in order to explore the specific molecular mechanism of TNC in DKD and bring a new direction for the treatment of DKD.METHODS The expression level of TNC in the serum of diabetic patients was detected by enzyme-linked immunosorbent assay(ELISA),the protein expression level of TNC in the glomerular area of DKD rats was detected by immunohistochemistry,and the expression level of TNC in the rat serum was detected by ELISA.Rat glomerular mesangial cells were cultured.Following high glucose stimulation,the expression levels of related proteins and mRNA were detected by Western blot and polymerase chain reaction,respectively.RESULTS ELISA results revealed an increase in the serum TNC level in patients with T2DM.Increasing UACR and hypertension significantly increased the expression of TNC(P<0.05).TNC expression was positively correlated with glycosylated haemoglobin(HbA1c)level,body mass index,systolic blood pressure,and UACR(P<0.05).Immunohistochemical staining showed that TNC expression in the glomeruli of rats w