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靶向SMAD7的微小RNA在糖尿病肾病发病机制中的治疗潜力

Therapeutic potential of SMAD7 targeting miRNA in the pathogenesis of diabetic nephropathy.

作者信息

Pooja Rathan V, Bhuvaneshwari K, Nideesh Adit G, Kavyashree S, Thulasi N, Geetha A V S, Milan K L, Ramkumar K M

机构信息

Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, 603 203, Tamil Nadu, India.

Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, 603 203, Tamil Nadu, India.

出版信息

Arch Biochem Biophys. 2025 Feb;764:110265. doi: 10.1016/j.abb.2024.110265. Epub 2024 Dec 10.

Abstract

Diabetic nephropathy (DN) is a common complication of diabetes and a leading cause of end-stage renal disease, characterized by progressive kidney fibrosis and inflammation. The transforming growth factor-beta (TGF-β) signaling pathway plays a crucial role in the pathogenesis of diabetes nephropathy, and SMAD7 is a key negative regulator of this pathway. Recent studies have highlighted the involvement of miRNA in the progression of DN. Computational analysis identified 11 potential miRNAs such as miR-424, miR-195, miR-216a, miR-503, miR-15a-5p, miR-15b-5p, miR-665, miR-520h, miR16-5p, miR-21 and miR-32-5p which are predicted to target 3'UTR of SMAD7 mRNA. This review aims to explore the role of these miRNAs in the progression of DN. Notably, these miRNAs have shown therapeutic potential in mitigating fibrosis and inflammation by modulating SMAD7 expression in DN. Future directions can be to investigate the mechanistic pathways through which these miRNAs exert their effects, as well as optimizing delivery systems for effective clinical application. Targeting miRNAs that modulate SMAD7 expression represents a promising strategy for developing specific and effective therapies for diabetic nephropathy.

摘要

糖尿病肾病(DN)是糖尿病常见的并发症,也是终末期肾病的主要原因,其特征为进行性肾纤维化和炎症。转化生长因子-β(TGF-β)信号通路在糖尿病肾病的发病机制中起关键作用,而SMAD7是该通路的关键负调节因子。最近的研究强调了miRNA在DN进展中的作用。通过计算分析确定了11种潜在的miRNA,如miR-424、miR-195、miR-216a、miR-503、miR-15a-5p、miR-15b-5p、miR-665、miR-520h、miR16-5p、miR-21和miR-32-5p,它们被预测靶向SMAD7 mRNA的3'UTR。本综述旨在探讨这些miRNA在DN进展中的作用。值得注意的是,这些miRNA通过调节DN中SMAD7的表达,在减轻纤维化和炎症方面显示出治疗潜力。未来的研究方向可以是研究这些miRNA发挥作用的机制途径,以及优化递送系统以实现有效的临床应用。靶向调节SMAD7表达的miRNA是开发糖尿病肾病特异性有效疗法的一种有前景的策略。

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