医学分子生物学杂志2026，Vol.23Issue(4)：389-397,9.DOI:10.3870/j.issn.1672-8009.2026.04.003
Diaph1基因在阿霉素诱导的肾脏损伤中的保护作用
The Protective Role of Diaph1 Gene in Adriamycin-induced Renal In-jury
摘要
Abstract
Objective To explore the key role of diaphanous-related formin 1(Diaph1)gene in the kidneys of nephropathy model mice.Methods Wild-type(WT),heterozygous(Diaph1+/-),and homozygous(Diaph1-/-)mice were used to establish the control group and the adriamycin model group,respectively,with 7 mice in each group.Mice in the adriamycin model group received adriamycin via tail vein injection,while those in the control group were administered an equal volume of normal saline.The Diaph1 gene was globally knocked out in mice using the CRISPR/Cas9 system,and homozygous mice were obtained by breeding heterozygous litterma-tes.Genotyping was performed by polymerase chain reaction(PCR).Hematoxylin and eosin(HE)staining was used to observe renal morphology in each group.Immunofluorescence staining was applied to detect the expression of Diaph1 in glomeruli and surrounding renal tubules.Serum and urinary albumin levels were measured using a microplate reader method,and creatinine levels were determined by the sarcosine oxidase method.Western blotting was performed to assess Diaph1 protein expression in the renal cortex.Quantitative real-time polymerase chain reaction(qRT-PCR)was conducted to detect the mRNA expression levels of Podocin,CD2-associated protein(Cd2ap),Nephrin,and kin of IRRE-like protein 1(Neph1)in mouse kidneys.Results In wild-type mice,compared with the control group,the adriamycin model group showed significantly decreased body weight(P＜0.05)and narrowed glomerular capsule spaces.Biochemical assays revealed elevated urinary albumin(P＜0.05)and serum creatinine(P＜0.05),along with reduced urinary creati-nine(P＜0.05).At the molecular level,both mRNA and protein expression of Diaph1 were sig-nificantly upregulated in the adriamycin model group(P＜0.05).In the Diaph1-knockout mice,compared with adriamycin-treated wild-type mice,adriamycin-treated heterozygous(Diaph1+/-)and homozygous(Diaph1-/-)mice exhibited aggravated glomerulosclerosis and further narrowed glomerular capsule spaces.Moreover,renal mRNA expression of Podocin,Cd2ap,and Nephrin was significantly decreased in adriamycin-treated Diaph1-/-mice(P＜0.05),and biochemical a-nalysis showed significantly reduced serum albumin and serum creatinine levels in these mice(P＜0.05).Conclusion The Diaph1 gene exerts a critical protective role in renal podocytes and tubu-lar epithelial cells,suggesting that Diaph1 is a potential functional gene in the adriamycin-induced nephropathy model.This provides new insights and directions for the treatment and future research of nephrotic syndrome.关键词
肾病综合征/透明形成素相关蛋白1/阿霉素/Diaph1基因敲除小鼠Key words
nephrotic syndrome/diaphanous-related formin 1/adriamycin/Diaph1 gene knockout mice分类
医药卫生引用本文复制引用
郭枭,刘悦石,庞聪,张学明,王昆,刘心洁,张玉杰,李向南..Diaph1基因在阿霉素诱导的肾脏损伤中的保护作用[J].医学分子生物学杂志,2026,23(4):389-397,9.基金项目
内蒙古自治区自然科学基金(No.2025QN03114),包头医学院博士科研启动基金(No.BYJJ-BSJJ202408、No.BYJJ-GCC202510),包头市青年创新人才项目(No.00123320),包头医学院花蕾计划(No.HLJH202516),包头医学院科学研究发展基金项目(No.BYJJ-QCJH202601) This work was supported by grants from Natural Science Foundation of Inner Mongolia Autonomous Region of China(No.2025QN03114),Baotou Medi-cal College Scientific Research Fund-Doctoral Research Fund(No.BYJJ-BSJJ202408,No.BYJJ-GCC202510),Baotou City Youth Innovation Talent Project Fund(No.00123320),Baotou Medical College Bud Plan(No.HLJH202516),and Baotou Medical College Scientific Research Development Fund Project(No.BYJJ-QCJH202601). （No.2025QN03114）
