Renal interstitial fibrosis (RIF) is a major manifestation of diabetic kidney disease (DKD). This study aimed to elucidate the specific mechanism by which miR-29a-3p affects RIF in DKD through Forkhead box protein 1 (FOXP1)-mediated TGF-β1/Smad3 and to provide novel ideas and therapeutic targets for RIF. Cell and animal models were constructed, and CCK-8, flow cytometry, Western blotting, immunofluorescence, RT‒qPCR, Masson's trichrome staining, hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining, Sirius red staining, and immunohistochemistry were used to detect the related indicators of RIF in DKD. The interaction between miR-29a-3p and FOXP1 was confirmed using a dual-luciferase assay. These findings suggested that miR-29a-3p can act on renal interstitial fibrosis cells in DKD through the TGF-β1/Smad3 signaling pathway mediated by FOXP1. The overexpression of miR-29a-3p inhibited the expression of fibrin-associated proteins in renal tissue, contracted the mesangial matrix and decreased the accumulation of renal fibrils to ultimately alleviate RIF in DKD. This study is the first to propose the specific molecular mechanism of miR-29a-3p in renal interstitial cells in DKD, which provides novel targets and strategies for the clinical treatment of RIF-related DKD.

Keywords: Diabetic kidney disease; FOXP1; Renal interstitial fibrosis; TGF-β1/Smad3; miR-29a-3p.

© The Author(s), under exclusive licence to Springer Nature B.V. 2025. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

肾间质纤维化（RIF）是糖尿病肾脏疾病（DKD）的主要表现形式。本研究旨在阐明miR-29a-3p通过叉头盒蛋白1（FOXP1）介导的TGF-β1/Smad3信号通路对DKD中RIF的影响的具体机制，并为RIF提供新的治疗思路和靶点。构建了细胞和动物模型，使用CCK-8、流式细胞术、Western blotting、免疫荧光、RT‒qPCR、Masson三色染色、苏木精-伊红（HE）和PAS染色、Sirius red染色以及免疫组化检测DKD中RIF的相关指标。通过双荧光素酶报告基因实验验证了miR-29a-3p与FOXP1之间的相互作用。研究结果表明，miR-29a-3p可以通过FOXP1介导的TGF-β1/Smad3信号通路影响DKD中的肾间质纤维化细胞。过表达miR-29a-3p可以抑制肾组织中纤维相关蛋白的表达，收缩基底膜和系膜基质，并减少肾小管内纤维沉积，最终缓解DKD中的RIF。本研究首次提出了miR-29a-3p在DKD肾间质细胞中的具体分子机制，为临床治疗与RIF相关的DKD提供了新的靶点和策略。

关键词：糖尿病肾脏疾病；FOXP1；肾间质纤维化；TGF-β1/Smad3；miR-29a-3p.

© The Author(s), under exclusive licence to Springer Nature B.V. 2025. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.