Oxymatrine Inhibits Twist-Mediated Renal Tubulointerstitial Fibrosis by Upregulating Id2 Expression
Oxymatrine Inhibits Twist-Mediated Renal Tubulointerstitial Fibrosis by Upregulating Id2 Expression
复制标题
氧化苦参碱通过上调 Id2 表达抑制扭转介导的肾小管间质纤维化
DOI：
10.3389/fphys.2020.00599
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发表时间：
2020-06-19
影响因子：
4
通讯作者：
Guo, Bing
中科院分区：
文献类型：
--
作者：
Xiao, Ying;Peng, Can;Guo, Bing
糖尿病肾病（DN）发展为慢性肾功能衰竭的最终途径是肾小球硬化和肾小管间质纤维化。DN早期可出现肾小管损害。大量研究表明，氧化苦参碱（OMT）具有多种生物学和药理学特性。近年来，OMT对器官纤维化的预防和治疗作用越来越受到重视。在本实验中，db/db小鼠腹腔注射OMT 120 mg/kg，持续8周，NRK-52 E与30 mmol/L葡萄糖和0.1 mg/mL OMT一起培养48 h。我们通过Western blot、Real-time PCR、免疫荧光、细胞转染、免疫共沉淀和荧光素酶等方法研究了NRK-52 E细胞中Id 2和Twist的关系以及OMT对E-cadherin、α-SMA、Fibronectin和Collagen-IV表达的影响。在体外和体内高糖条件下，OMT可增加Id 2的表达，但降低Twist的表达。Id 2的恢复促进了其与Twist的结合，并影响了E-cadherin的活性，抑制EMT和ECM的过度增殖和异常沉积。总之，OMT通过与Twist结合并影响其下游靶基因的转录激活，促进Id 2逆转糖尿病肾小管上皮细胞EMT，发挥抗纤维化作用。这一发现为延缓糖尿病肾纤维化的进展和治疗提供了新的实验依据。
The final pathway for the development of diabetic nephropathy (DN) into chronic renal failure in DN is glomerulosclerosis and tubulointerstitial fibrosis. Renal tubular lesions can occur in the early stage of DN renal injury. Cumulative evidence shows that oxymatrine (OMT) has a variety of biological and pharmacological properties. In recent years, more attention has been paid on the preventive and therapeutic influence of OMT on organ fibrosis. In this experiment, db/db mice were intraperitoneally injected with OMT 120 mg/kg for 8 weeks, and NRK-52E cultured with 30 mmol/L glucose and 0.1 mg/mL OMT for 48-hour. We investigated the relationship between Id2 and Twist in NRK-52E cells and the effect of OMT on the expression of E-cadherin, α-SMA, Fibronectin, and Collagen-IV by Western blot, Real-time PCR, Immunofluorescence, cell transfection, Co-Immunoprecipitation, and Luciferase assays. OMT increased the expression of Id2 but decreased that of Twist under high glucose condition in vitro and in vivo. The promoted recovery of Id2 facilitated its binding to Twist and affected E-cadherin activity inhibiting EMT and the excessive proliferation and abnormal deposition of ECM. In brief, OMT promotes Id2 to reverse EMT and exert anti-fibrotic effect in diabetic renal tubular epithelial cells by binding Id2 to Twist and affecting its transcriptional activation of downstream target genes. Or findings provide a new experimental basis for delaying the progress and for treatment of diabetic renal fibrosis.