Subproteomic profiling from renal cortices in OLETF rats reveals mutations of multiple novel genes in diabetic nephropathy
Subproteomic profiling from renal cortices in OLETF rats reveals mutations of multiple novel genes in diabetic nephropathy
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OLETF 大鼠肾皮质的亚蛋白质组分析揭示了糖尿病肾病中多个新基因的突变
DOI：
10.1007/s13258-021-01174-0
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发表时间：
2021-10-13
期刊：
影响因子：
2.1
通讯作者：
Li，Ping
中科院分区：
文献类型：
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作者：
Li，Zhiguo;Shen，Hong;Li，Ping
糖尿病肾病（Diabetic nephropathy，DN）严重威胁人类健康，但其发病机制尚不完全清楚。本研究旨在通过对36周龄糖尿病OLETF大鼠和正常对照组Long-Evans德岛Otsuka（LETO）大鼠肾皮质蛋白表达谱的分析，探讨DN的发病机制。分离肾皮质。采用可溶性和不溶性高分辨亚蛋白质组学方法分离蛋白质，对差异蛋白质进行分析和鉴定。结果共发现36个差异表达蛋白质，其中11个蛋白质在OLETF和LETO大鼠间具有不同的等电点和分子量。进一步测序确定了编码这些蛋白质中的8种蛋白质的基因中的点突变，这些蛋白质参与与DN密切相关的许多生物学过程，包括氧化应激和炎症。结论本研究揭示了糖尿病OLETF大鼠多个新基因的突变，为DN的发病机制提供了新的潜在靶点，有助于更好地了解DN的发病机制。
BackgroundDiabetic nephropathy (DN) is a serious threat to human health, but its pathogenesis is not fully understood. Otsuka Long-Evans Tokushima Fatty (OLETF) rats are very similar to human DN in many aspects such as pathological changes and processes, and are deemed to be an ideal rodent model.ObjectiveThis study was aimed to explore the pathogenesis of DN by analyzing the protein expression profile from renal cortices in OLETF rats.MethodsThirty-six-week-old diabetic OLETF rats and normal control Long-Evans Tokushima Otsuka (LETO) rats were nephrectomized, and the renal cortices were isolated. The proteins were separated by soluble and insoluble high-resolution subproteomics methods for the analysis and identification of differential proteins.ResultsThirty-six differentially expressed proteins were found. Among them, 11 proteins had different isoelectric points and molecular weights between OLETF and LETO rats. Further sequencing identified point mutations in genes encoding eight of these proteins, which are involved in many biological processes closely related to DN, including oxidative stress and inflammation. Five of these eight proteins have not been reported in DN.ConclusionThis study reveals mutations of multiple novel genes in diabetic OLETF rats, providing some new potential targets for the pathogenesis of DN and helping to better understand the pathogenesis of DN.