Department of Endocrinology, Xijing Hospital, Air Force Medical University, No.127 Changle West Road, Xi'an, 710032, China.
Department of Pharmacology, Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medical of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Air Force Medical University, Xi'an, 710032, China.
J Endocrinol Invest. 2024 Jun;47(6):1531-1544. doi: 10.1007/s40618-023-02253-7. Epub 2023 Dec 26.
Palmitic acid (PA), the major saturated fatty acid in the blood, often induces the initiation and progression of diabetic kidney disease (DKD). However, the underlying mechanism remains unclear. DACH1 is an important regulator of kidney functions. Herein, we investigated the roles of DACH1 in PA-induced kidney injury.
Clinical data from the NHANES database were subjected to analyse the association between serum PA (sPA), blood glucose and kidney function. Molecular docking of PA was performed with DACH1. Immunohistochemistry, cell viability, annexin V/7-AAD double staining, TUNEL assay, immunofluorescent staining, autophagic flux analysis, qRT-PCR and western blot were performed.
Clinical data confirmed that sPA was increased significantly in the pathoglycemia individuals compared with controls and correlated negatively with renal function. Our findings suggested that PA could dock with DACH1. DACH1 enhances cell viability by inhibiting apoptosis and attenuating autophagy blockage induced by PA. Furthermore, the results demonstrated that DACH1 ameliorated inflammation and fibrosis through TLR4/MyD88/NF-κB and TGF-β/Smad signalling pathway in PA-treated renal tubular epithelial cell line (HK-2).
This study proved that sPA presents a risk factor for kidney injuries and DACH1 might serve as a protective target against renal function deterioration in diabetic patients.
棕榈酸（PA）是血液中主要的饱和脂肪酸，常诱导糖尿病肾病（DKD）的发生和进展。然而，其潜在机制尚不清楚。DACH1 是肾脏功能的重要调节因子。本研究旨在探讨 DACH1 在 PA 诱导的肾脏损伤中的作用。
对 NHANES 数据库中的临床数据进行分析，以研究血清 PA（sPA）、血糖与肾功能之间的关系。采用分子对接研究 PA 与 DACH1 的结合。进行免疫组织化学、细胞活力、Annexin V/7-AAD 双重染色、TUNEL 检测、免疫荧光染色、自噬流分析、qRT-PCR 和 Western blot 实验。
临床数据证实，与对照组相比，血糖异常个体的 sPA 显著升高，且与肾功能呈负相关。研究结果提示 PA 可与 DACH1 结合。DACH1 通过抑制细胞凋亡和减轻 PA 诱导的自噬阻断来增强细胞活力。此外，研究结果表明，DACH1 通过 TLR4/MyD88/NF-κB 和 TGF-β/Smad 信号通路改善了 PA 处理的肾小管上皮细胞系（HK-2）中的炎症和纤维化。
本研究证明 sPA 是肾脏损伤的危险因素，DACH1 可能是糖尿病患者肾功能恶化的保护靶标。
