N6-Methyladenosine modification of circDcbld2 in Kupffer cells promotes hepatic fibrosis via targeting miR-144-3p/Et-1 axis

被引：0

作者：

Zhu, Sai ^{[1
,2
]}

Chen, Xin ^{[1
]}

Sun, Lijiao ^{[1
]}

Li, Xiaofeng ^{[1
]}

Chen, Yu ^{[3
]}

Li, Liangyun ^{[1
]}

Suo, Xiaoguo ^{[1
]}

Xu, Chuanhui ^{[1
]}

Ji, Minglu ^{[1
]}

Wang, Jianan ^{[1
]}

Wang, Hua ^{[1
]}

Zhang, Lei ^{[1
]}

Meng, Xiaoming ^{[1
]}

Huang, Cheng ^{[1
]}

Li, Jun ^{[1
]}

机构：

[1] Anhui Med Univ, Anhui Inst Innovat Drugs, Sch Pharm, Inflammat & Immune Mediated Dis Lab Anhui Prov, Hefei 230032, Peoples R China

[2] Anhui Med Univ, Affiliated Hosp 1, Dept Nephropathy, Hefei 230022, Peoples R China

[3] Bengbu Med Coll, Affiliated Hosp 2, Dept Pharm, Bengbu 233000, Peoples R China

来源：

ACTA PHARMACEUTICA SINICA B | 2025年 / 15卷 / 01期

基金：

中国博士后科学基金;

关键词：

Kupffer cells; circDcbld2; miR-144-3p; Et-1; N6-methyladenosine; Wtap; Igf2bp2; Hepatic fibrosis; LIVER FIBROSIS; REGULATORY ROLE; RNA; ACTIVATION; YAP1;

D O I：

10.1016/j.apsb.2024.11.003

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Kupffer cells (KCs), as residents and sentinels of the liver, are involved in the formation of hepatic fibrosis (HF). However, the biological functions of circular RNAs (circRNAs) in KCs to HF have not been determined. In this study, the expression levels of circRNAs, microRNAs, and messenger RNAs (mRNAs) in KCs from a mouse model of HF mice were investigated using microarray and circRNA-Seq analyses. circDcbld2 was identified as a candidate circRNA in HF, as evidenced by its up-regulation in KCs. Silver staining and mass spectrometry showed that Wtap and Igf2bp2 bind to cirDcbld2. The suppression of circDcbld2 expression decreased the KC inflammatory response and oxidative stress and inhibited hepatic stellate cell (HSCs) activation, attenuating mouse liver fibrogenesis. Mechanistically, Wtap mediated the N6-methyladenosine (m6A) methylation of circDcbld2, and Igf2bp2 recognized m6A-modified circDcbld2 and increased its stability. circDcbld2 contributes to the occurrence of HF by binding miR-144-3p/Et-1 to regulate the inflammatory response and oxidative stress. These findings indicate that circDcbld2 functions via the m6A/circDcbld2/miR-144-3p/Et-1 axis and may act as a potential biomarker for HF treatment. @ 2025 The Authors. Published by Elsevier B.V. on behalf of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

引用

页码：296 / 313

页数：18

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