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ACSL1:一项初步研究为治疗肾纤维化提供了新的靶点,可能为糖尿病肾病带来新的见解。

ACSL1: A preliminary study that provides a new target for the treatment of renal fibrosis could bring new insights in diabetic kidney disease.

机构信息

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, College of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China; Department of Pharmacy, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221004, China.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, College of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China.

出版信息

Nefrologia (Engl Ed). 2023 Dec;43 Suppl 2:38-46. doi: 10.1016/j.nefroe.2023.05.008. Epub 2024 Jan 19.

Abstract

BACKGROUND

Renal fibrosis is the main cause of the development of diabetic kidney disease (DKD). ACSL1 plays an important role in colon cancer and liver fibrosis.

METHODS

We screened ACSL1 by proteomics analysis and then verified the expression of ACSL1 in the urine of diabetic nephropathy patients by WB and ELISA. Then, a total of 12db/m and db/db mice were used to verify the association between renal fibrosis and ACSL1. Periodic acid-Schiff (PAS) staining, Masson staining, and immunostaining were performed for histological studies. The relationship between ACSL1 and renal fibrosis was studied by knocking down ACSL1 in cell experiments.

RESULTS

The expression of ACSL1 was significantly increased in the exfoliated urine cells and urine supernatant of diabetic nephropathy patients and was closely related to renal function. In addition, the expression of ACSL1 was significantly increased in the renal tissues of db/db mice with fibrosis. Knocking down ACSL1 in HK-2 cells was shown to reverse renal fibrosis induced by high glucose.

CONCLUSIONS

We found a potential therapeutic target for preventing or ameliorating the progression of DKD fibrosis. Reducing ACSL1 expression may be a new strategy for the treatment of renal fibrosis caused by DKD, which provides an experimental theoretical basis for new drug research.

摘要

背景

肾纤维化是糖尿病肾病(DKD)发展的主要原因。ACSL1 在结肠癌和肝纤维化中发挥重要作用。

方法

我们通过蛋白质组学分析筛选 ACSL1,然后通过 WB 和 ELISA 验证 ACSL1 在糖尿病肾病患者尿液中的表达。然后,使用总共 12 只 db/m 和 db/db 小鼠验证肾脏纤维化与 ACSL1 之间的关联。进行过碘酸希夫(PAS)染色、Masson 染色和免疫染色进行组织学研究。通过在细胞实验中敲低 ACSL1 研究 ACSL1 与肾纤维化之间的关系。

结果

糖尿病肾病患者脱落的尿液细胞和尿液上清液中 ACSL1 的表达明显增加,与肾功能密切相关。此外,db/db 小鼠纤维化肾组织中 ACSL1 的表达明显增加。在 HK-2 细胞中敲低 ACSL1 可逆转高糖诱导的肾纤维化。

结论

我们发现了一种预防或改善 DKD 纤维化进展的潜在治疗靶点。降低 ACSL1 的表达可能是治疗 DKD 引起的肾纤维化的新策略,为新药研究提供了实验理论基础。

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