| The m6A reader IGF2BP2 regulates glycolytic metabolism and mediates histone lactylation to enhance hepatic stellate cell activation and liver fibrosis | |
Zhou, Yongqiang1; Yan, Jiexi1,2; Huang, He1; Liu, Lu3; Ren, Longfei4; Hu, Jinjing5; Jiang, Xiaoxu1; Zheng, Yan1; Xu, Lingcong1; Zhong, Fupeng1; Li, X(李汛)1,2,4,5 | |
| 2024-03-05 | |
| Source Publication | Cell Death & Disease Impact Factor & Quartile Of Published Year The Latest Impact Factor & Quartile |
| ISSN | 2041-4889 |
| Volume | 15Issue:3 |
| page numbers | 16 |
| Abstract | Evidence for the involvement of N-6-Methyladenosine (m(6)A) modification in the etiology and progression of liver fibrosis has emerged and holds promise as a therapeutic target. Insulin-like growth factor 2 (IGF2) mRNA-binding protein 2 (IGF2BP2) is a newly identified m(6)A-binding protein that functions to enhance mRNA stability and translation. However, its role as an m(6)A-binding protein in liver fibrosis remains elusive. Here, we observed that IGF2BP2 is highly expressed in liver fibrosis and activated hepatic stellate cells (HSCs), and inhibition of IGF2BP2 protects against HSCs activation and liver fibrogenesis. Mechanistically, as an m(6)A-binding protein, IGF2BP2 regulates the expression of Aldolase A (ALDOA), a key target in the glycolytic metabolic pathway, which in turn regulates HSCs activation. Furthermore, we observed that active glycolytic metabolism in activated HSCs generates large amounts of lactate as a substrate for histone lactylation. Importantly, histone lactylation transforms the activation phenotype of HSCs. In conclusion, our findings reveal the essential role of IGF2BP2 in liver fibrosis by regulating glycolytic metabolism and highlight the potential of targeting IGF2BP2 as a therapeutic for liver fibrosis. |
| Publisher | SPRINGERNATURE |
| DOI | 10.1038/s41419-024-06509-9 |
| Indexed By | SCIE |
| Language | 英语 |
| WOS Research Area | Cell Biology |
| WOS Subject | Cell Biology |
| WOS ID | WOS:001180295000003 |
| Original Document Type | Article |
| PMID | 38443347 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://ir.lzu.edu.cn/handle/262010/585131 |
| Collection | 第一临床医学院 |
| Affiliation | 1.Lanzhou Univ, Sch Clin Med 1, Lanzhou, Peoples R China; 2.Lanzhou Univ, Precis Med Ctr, Hosp 1, Lanzhou, Peoples R China; 3.Lanzhou Univ, Dept Pediat, Hosp 1, Lanzhou, Peoples R China; 4.Lanzhou Univ, Dept Gen Surg, Hosp 1, Lanzhou, Peoples R China; 5.Key Lab Biotherapy & Regenerat Med Gansu Prov, Lanzhou, Peoples R China |
| First Author Affilication | First Clinical School |
| First Signature Affilication | First Clinical School |
| Recommended Citation GB/T 7714 | Zhou, Yongqiang,Yan, Jiexi,Huang, He,et al. The m6A reader IGF2BP2 regulates glycolytic metabolism and mediates histone lactylation to enhance hepatic stellate cell activation and liver fibrosis[J]. Cell Death & Disease,2024,15(3). |
| APA | Zhou, Yongqiang.,Yan, Jiexi.,Huang, He.,Liu, Lu.,Ren, Longfei.,...&Li, Xun.(2024).The m6A reader IGF2BP2 regulates glycolytic metabolism and mediates histone lactylation to enhance hepatic stellate cell activation and liver fibrosis.Cell Death & Disease,15(3). |
| MLA | Zhou, Yongqiang,et al."The m6A reader IGF2BP2 regulates glycolytic metabolism and mediates histone lactylation to enhance hepatic stellate cell activation and liver fibrosis".Cell Death & Disease 15.3(2024). |
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