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Subproteomic profiling from renal cortices in OLETF rats reveals mutations of multiple novel genes in diabetic nephropathy

Genes & Genomics 2022년 44권 1호 p.109 ~ 122
Li Zhiguo, Shen Hong, Liu Yeqiang, Zhou Xuefeng, Yan Meihua, He Hailan, Zhao Tingting, Zhang Haojun, Li Ping,
소속 상세정보
 ( Li Zhiguo ) - North China University of Science and Technology School of Public Health
 ( Shen Hong ) - North China University of Science and Technology Department of Modern Technology and Education
 ( Liu Yeqiang ) - North China University of Science and Technology Kailuan General Hospital Department of Endocrinology
 ( Zhou Xuefeng ) - China-Japan Friendship Hospital Institute of Clinical Medical Science
 ( Yan Meihua ) - China-Japan Friendship Hospital Institute of Clinical Medical Science
 ( He Hailan ) - North China University of Science and Technology School of Graduate Studies
 ( Zhao Tingting ) - China-Japan Friendship Hospital Institute of Clinical Medical Science
 ( Zhang Haojun ) - China-Japan Friendship Hospital Institute of Clinical Medical Science
 ( Li Ping ) - China-Japan Friendship Hospital Institute of Clinical Medical Science

Abstract


Background: Diabetic 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.

Objective: This study was aimed to explore the pathogenesis of DN by analyzing the protein expression profile from renal cortices in OLETF rats.

Methods: Thirty-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.

Results: Thirty-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.

Conclusion: This 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.

키워드

Diabetic nephropathy; Proteomics; Two-dimensional difference gel electrophoresis; Gene mutation; OLETF rat

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