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不同严重程度糖尿病肾病患者循环 TGFβ 调节 miRNA 的相互作用。

Interaction of circulating TGFβ regulatory miRNAs in different severity of diabetic kidney disease.

机构信息

Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, Liaoning, China.

Department of Endocrinology, The Second Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.

出版信息

Arch Physiol Biochem. 2024 Jun;130(3):285-299. doi: 10.1080/13813455.2022.2034884. Epub 2022 Feb 11.

DOI:10.1080/13813455.2022.2034884
PMID:35147479
Abstract

AIMS

To explore the interaction of TGFβ regulatory microRNAs (miRNAs) with different severities of diabetic kidney disease (DKD).

METHODS

According to different UACR (30 and 300 mg/g), 436 subjects were included, and high glucose induced RMCs were cultured. Real-time PCR, ELISA, and automatic biochemical analysis were used to measure miRNAs, TGFβ1, and other biochemical indicators in serum and RMCs. Target genes of miRNA were predicted and visualised by bioinformatics.

RESULTS

HbA1c, TGFβ1, miR-217, and miR-224 in T2DM patients increased with UACR, while miR-192 and miR-216a decreased. Ln UACR was positively correlated with HbA1c, TGFβ1, miR-217, and miR-224, and negatively correlated with miR-192 and miR-216a. High glucose and TGFβ1 affected miRNAs and these miRNAs affected each other. The miRNA target genes mainly revolve around PTEN, PI3K/Akt, and MAPK signalling pathways.

CONCLUSION

TGFβ regulatory miRNAs and different severity of DKD have a potential interaction regulating fibrosis through PTEN, PI3K/Akt, and MAPK pathways.

摘要

目的

探讨转化生长因子β(TGFβ)调节 microRNAs(miRNAs)与不同严重程度糖尿病肾病(DKD)的相互作用。

方法

根据不同的尿白蛋白肌酐比值(UACR,30 和 300mg/g),纳入 436 例受试者,并培养高糖诱导的大鼠肾小球系膜细胞(RMCs)。实时 PCR、ELISA 和自动生化分析用于测量血清和 RMCs 中的 miRNAs、TGFβ1 和其他生化指标。通过生物信息学预测和可视化 miRNA 的靶基因。

结果

T2DM 患者的 HbA1c、TGFβ1、miR-217 和 miR-224 随 UACR 增加而升高,而 miR-192 和 miR-216a 则降低。Ln UACR 与 HbA1c、TGFβ1、miR-217 和 miR-224 呈正相关,与 miR-192 和 miR-216a 呈负相关。高糖和 TGFβ1 影响 miRNAs,这些 miRNAs 相互影响。miRNA 靶基因主要集中在 PTEN、PI3K/Akt 和 MAPK 信号通路。

结论

TGFβ 调节 miRNAs 与不同严重程度的 DKD 之间存在潜在的相互作用,通过 PTEN、PI3K/Akt 和 MAPK 通路调节纤维化。

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