Diosgenin Improves Lipid Metabolism in Diabetic Nephropathy via Regulation of miR-148b-3p/DNMT1/FOXO1 Axis

被引：1

作者：

Luo, Min ^{[1
,2
,3
]}

Hu, Zongren ^{[1
,2
,4
]}

Yang, Jichang ^{[1
,2
,5
]}

Yang, Jinhan ^{[1
,2
,5
]}

Sheng, Wen ^{[4
]}

Lin, Chengxiong ^{[6
]}

Li, Dian ^{[7
]}

He, Qinghu ^{[1
,2
,4
]}

机构：

[1] Hunan Univ Med, Hunan Engn Res Ctr Internet Chinese & Western Med, Huaihua, Peoples R China

[2] Hunan Univ Med, Affiliated Hosp 1, Dept Tradit Chinese Med, Huaihua, Peoples R China

[3] Cent South Univ, Xiangya Hosp 2, Dept Nephrol, Changsha, Peoples R China

[4] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Peoples R China

[5] Gooeto Internet Based Hosp, Changsha, Peoples R China

[6] Huairen Hosp Tradit Chinese Med, Huaihua, Peoples R China

[7] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Ophthalmol, Changsha, Peoples R China

来源：

NEPHRON | 2025年 / 149卷 / 04期

基金：

中国国家自然科学基金;

关键词：

Diosgenin; MiR-148b-3p; DNMT1; Lipid metabolism; Diabetic nephropathy; ACCUMULATION; APOPTOSIS;

D O I：

10.1159/000541690

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Background: The progression of diabetic nephropathy (DN) is closely associated with lipid accumulation. Diosgenin (Dio) plays a beneficial role in the lipid metabolism associated with multiple diseases. Thus, the mechanism underlying Dio's function in DN associated with aberrant lipid accumulation warrants further investigation. Methods: To model DN in vitro, HK-2 cells were treated with high glucose (HG) and palmitic acid. Cell viability was evaluated using MTT assay. The triglyceride (TG) content in HK-2 cells was measured using a commercial assay kit. The formation of lipid droplets in HK-2 cells was observed using Oil Red O staining. The expression levels of mRNA and protein were detected using RT-qPCR and Western blot, respectively. The DNA methylation of FOXO1 was assessed using MSP. The interaction between DNMT1 and the FOXO1 promoter was confirmed by ChIP assay. Results: Dio treatment reduced TG levels and lipid droplet formation in HK-2 cells co-treated with HG and palmitic acid. Simultaneously, the levels of miR-148b-3p and FOXO1 were increased by Dio, while Dio decreased the expression levels of DNMT1 and SREBP-2. Meanwhile, miR-148b-3p can bind to DNMT1, which in turn inhibits the expression of FOXO1 by mediating the DNA methylation of FOXO1. In addition, FOXO1 negatively regulates the expression of SREBP-2 by interacting with the SREBP-2 promoter. MiR-148b-3p inhibition or silencing of FOXO1 abolished the inhibitory effect of Dio on TG production and lipid droplet formation. This effect was further exacerbated by the downregulation of DNMT1. FOXO1 overexpression may counteract the promotive effects of miR-148b-3p inhibitor on lipid accumulation. Conclusions: Dio treatment reduced TG production and lipid droplet formation in HK-2 cells during the progression of DN by modulating the miR-148b-3p/DNMT1/FOXO1/SREBP-2 axis. This finding provides new evidence supporting the therapeutic potential of Dio for DN.

引用

页码：226 / 239

页数：14

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