Circ_0054633沉默通过调节MiR-136-5p/SMAD3信号传导抑制高血糖诱导的肾系膜细胞细胞外基质积累

IF 5.9 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Qing Jiang , Hongxin Chen , Ke Wang , Xiaowei Zhu , Jun Yin , Wei Tang
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引用次数: 0

摘要

糖尿病肾病(DKD)是糖尿病(DM)最常见的并发症,肾小球系膜细胞产生的细胞外基质(ECM)过度沉积是其重要标志。环状RNA circ_0054633是一种很有前景的糖尿病生物标志物;然而,这种环状RNA在DKD中的作用尚不清楚。本研究招募了10名健康对照(CT)、10名糖尿病患者和10名DKD患者,分析了血清circ_0054633的表达。Circ_0054633水平在CT、DM、DKD组逐渐升高,且与血清白蛋白/尿肌酐比值及纤维化程度相关。体外实验表明,circ_0054633沉默可显著降低高血糖应激诱导的细胞增殖和人肾系膜细胞ECM积累。体内实验表明circ_0054633在db/db小鼠肾中沉默可抑制肾纤维化。机制上,circ_0054633沉默通过释放miR-136-5p发挥作用,miR-136-5p随后下调SMAD3。本研究可能证明circ_0054633的临床意义,它可能是未来DKD治疗的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Circ_0054633 silencing suppresses hyperglycemia-induced extracellular matrix accumulation in renal mesangial cells by regulating MiR-136-5p/SMAD3 signaling
Diabetic kidney disease (DKD) is the most common complication of diabetes mellitus (DM), with excessive deposition of the extracellular matrix (ECM) produced by glomerular mesangial cells being its critical hallmark. circ_0054633, a circular RNA, is a promising biomarker for DM; however, the role of this circular RNA in DKD remains unknown. This study enrolled 10 healthy controls (CT), 10 DM patients, and 10 DKD patients, and serum circ_0054633 expression was analyzed. Circ_0054633 levels gradually increased in the CT, DM, and DKD groups, which also correlated with the serum indicator albumin/urine creatinine ratio and the degree of fibrosis. In vitro experiments, circ_0054633 silencing markedly attenuated hyperglycemia stress-induced cell proliferation and ECM accumulation in human renal mesangial cells). In vivo experiments indicated that circ_0054633 silencing in the db/db mouse kidney suppressed renal fibrosis. Mechanistically, circ_0054633 silencing exerted its effect by releasing miR-136-5p, which then downregulated SMAD3. The present study possibly demonstrates the clinical significance of circ_0054633, which may be a target for future DKD treatment.
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来源期刊
Non-coding RNA Research
Non-coding RNA Research Medicine-Biochemistry (medical)
CiteScore
7.70
自引率
6.00%
发文量
39
审稿时长
49 days
期刊介绍: Non-coding RNA Research aims to publish high quality research and review articles on the mechanistic role of non-coding RNAs in all human diseases. This interdisciplinary journal will welcome research dealing with all aspects of non-coding RNAs-their biogenesis, regulation and role in disease progression. The focus of this journal will be to publish translational studies as well as well-designed basic studies with translational and clinical implications. The non-coding RNAs of particular interest will be microRNAs (miRNAs), small interfering RNAs (siRNAs), small nucleolar RNAs (snoRNAs), U-RNAs/small nuclear RNAs (snRNAs), exosomal/extracellular RNAs (exRNAs), Piwi-interacting RNAs (piRNAs) and long non-coding RNAs. Topics of interest will include, but not limited to: -Regulation of non-coding RNAs -Targets and regulatory functions of non-coding RNAs -Epigenetics and non-coding RNAs -Biological functions of non-coding RNAs -Non-coding RNAs as biomarkers -Non-coding RNA-based therapeutics -Prognostic value of non-coding RNAs -Pharmacological studies involving non-coding RNAs -Population based and epidemiological studies -Gene expression / proteomics / computational / pathway analysis-based studies on non-coding RNAs with functional validation -Novel strategies to manipulate non-coding RNAs expression and function -Clinical studies on evaluation of non-coding RNAs The journal will strive to disseminate cutting edge research, showcasing the ever-evolving importance of non-coding RNAs in modern day research and medicine.
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